MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Stimulace angiogeneze

3-Mercaptopyruvate sulfurtransferase

  • Supports endothelial cell angiogenesis and bioenergetics

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3)

  • Key glycolytic regulator
  • Regulates angiogenesis by controlling the balance of tip versus stalk cells
  • Endothelial cells acquire a tip cell phenotype
    • They increase glycolytic production of ATP for sprouting
  • Pharmacological blockade of PFKFB3
    • Causes a transient, partial reduction in glycolysis
    • Reduces pathological angiogenesis with minimal systemic harm

Inhibice asymmetric dimethylarginine (ADMA)


Achillea Achillea fragrantissima (Forssk.) Sch. Bip.

  • Rostliny krytosemenné » třída Rosopsida - vyšší dvouděložné rostliny » řád Asterales - hvězdnicotvaré » čeleď Asteraceae - hvězdnicovité » rod Achillea - řebříček
  • Ethanol Extract
  • Enhances Angiogenesis through Stimulation of VEGF Production
  • In concentrations of 50 and 100 mcg/ml
  • Significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings
  • In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner
  • 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment
    • Applied on rat excision wounds for six days
    • Effective in wound healing and maturation of the scar
  • www.eurekaselect.com/189633/article

Adiponectin


Aloe vera gel

  • Promote wound healing, pro-angiogenesis in the wound skin and a CAM model

Beta-sitosterol of A. vera gel

  • Potent pro-angiogenic activity in the CAM assay
  • Stimulated neovascularization in the Matrigel plug assay with the presence of heparin in mouse
  • Promoted pro-angiogenesis in the ischemia/reperfusion-damaged brain of Mongolian gerbil through different factors
    • VEGF, VEGF receptor Flk1, von Willebrand factors, and blood vessel matrix laminin
  • Intraperitoneal administration of beta-sitosterol at 500 microg/kg/day for a period of 19 days
    • Significantly improved the motion recovery of ischaemia/reperfusion-damaged gerbils
      • Assessed by rota-rod testing
  • pubmed.ncbi.nlm.nih.gov/11988857/
  • Aloe vera gel and its extracts
    • Angiogenic on the chorioallantoic membrane (CAM) of chick embryo
  • Aloe vera gel, beta-sitosterol
    • Showed a potent angiogenic activity in the CAM assay
  • In the presence of heparin, beta-sitosterol stimulated neovascularization
    • In the mouse Matrigel plug assay and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay
  • Beta-sitosterol is a novel plant-derived angiogenic factor
    • Potential pharmaceutical applications for the management of chronic wounds
  • pubmed.ncbi.nlm.nih.gov/14517429/

Angelica sinensis - Andělika čínská (děhel čínský) - Dong Quai


Angiogenic gel substrate (Matrigel pellet assay)

  • V pokusech injikován s.c. myším

Angs

  • protein family consisting of Ang-1, Ang-2, Ang-3, and Ang-4
  • Different functions in angiogenesis
  • Ang-1 and -4
    • Can bind to TIE2 and stimulate the tyrosine phosphorylation of TIE2
  • Ang-2 and -3
    • Can competitive combined TIE2 without stimulating tyrosine phosphorylation
      • Stopping the signal transduction of angiogenesis (Sallinen et al., 2010; Lin et al., 2011; Sallinen et al., 2014)
  • Ang-1, Ang-2
    • Block the TIE2 signaling
  • Ang-2
    • Induce the TIE2 signaling without Ang-1 (Yuan et al., 2009)
    • Ang-2 destabilize the stabilized vessel (Tse et al., 2003).
  • Ang-1
    • Promotes the maturation and stabilization of vessel
  • www.frontiersin.org/articles/10.3389/fcell.2020.00758/full

Astragalus membranaceus Bunge

  • Pro-angiogenic properties in vivo models [Zhou]

Calycosin and formononetin

  • Pro-angiogenic stimulators both from Radix Astragali
  • Calycosin promoted sprouts formation
    • Via VEGF, FGF, and ErbB signaling pathways
  • [Zhou]

Astragaloside IV

  • Saponin from Radix Astragali
  • Promoted cell proliferation, migration, and tube formation in HUVECs via activation:
    • VEGF/VEGFR2/KDR/Flk1/Akt, JAK2/STAT3, (ERK1/2) and upregulation of eNOS expression and nitric oxide (NO) production
  • Induced an angiogenic response in a transgenic zebrafish model in vivo
-[Zhou]

Astragalus membranaceus extract

  • Promotes neovascularisation by VEGF pathway in rat model of ischemic injury.

Becaplermin (Regranex, recombinant human PDGF-BB)

  • For diabetic foot ulcer disease in 1977
  • Was the first angiogenesis-stimulating drug that was used as a therapeutic angiogenesis approach.

Beta 2-Adrenergic Receptor Stimulation

  • Improves Endothelial Progenitor Cell–Mediated Ischemic Neoangiogenesis
  • Stimulation induced a
    • Significant increase of cell proliferation,
    • Improved the EPCs migratory activity,
    • Enhanced the EPCs’ ability to promote endothelial cell network formation in vitro

In vivo studies in animals model of hindlimb ischemia

  • Treatment resulted in an improvement of impaired angiogenic phenotype in beta 2AR KO mice after induction of ischemia
  • no significant amelioration was observed when beta 2AR knock out (KO)
  • Wild-type–derived EPCs’ injection resulted in
    • Significantly higher blood flow restoration in ischemic hindlimb
    • Higher capillaries density at histological analysis as compared with not treated or ß2AR KO EPC-treated mice
  • www.ahajournals.org/doi/10.1161/CIRCRESAHA.111.300152
  • Clebuterol
  • Isoprenalin
  • Salmeterol

Boswellia serrata

  • Wound healing potential via
    • Inhibition of oxido-inflammatory markers (oxido-nitrosative stress, TNF-?, interleukins, and nuclear factor-kappa-light-chain-enhancer of activated B cells)
    • Increased collagen synthesis (hydroxyproline and collagen-1) and angiogenesis (Ang-1/Tie2)
    • Promoting growth factors (transforming growth factor beta 1 and vascular endothelial growth factor)
    • Inhibition of apoptosis (Bcl-2-associated X protein)
  • To accelerate wound healing in experimental delayed diabetic foot ulcer
  • pubmed.ncbi.nlm.nih.gov/30909313/

Carthami Flos whole extract - Carthami tinctorii flos, světlice barvířská - květ

  • Pro-angiogenic properties in vivo models [Zhou]
  • Promoting cell proliferation, migration, and tube formation in HMEC cells in vitro
    • + numbers of sprouts in the sub-intestinal vessels (SIVs)
    • Upregulating angiogenesis-associated growth factors and receptors
      • IGF1, CTGF, NRP2, VEGFR3
    • Transcription factors
      • HIF1alpha
    • Factors for matrix degradation and cell migration
      • MMP2, MMP9, TIMP2, PLG, plasminogen factor urokinase
    • Molecules for cell adhesion
      • ITGAV, ITGB3, beta-catenin, and PECAM1
    • Factors for tubule formation
      • ANG1, TIE2, PDGFR-B, CDH5, S1PR1, FGF2, Shh, and TGFRB1
    • Factors for blood vessel maturation and formation
      • EPHB2
  • [Zhou]

Carthami Flos

  • Pro-angiogenic properties in vivo models [Zhou]

Co2 injekce - karoboxyterapie

Palas Athena Praha 11


Copper

  • Known to trigger endothelial cells towards angiogenesis
  • Angiogenic and healing potential of copper ions
  • Combination of CuSO4 with increasing doses of VEGF or FGF-2
    • Enhanced the complexity of angiogenic networks in a significant manner
  • FGF-2 with CuSO4 in a cylindrical collagen-based scaffold
    • CuSO4 enhanced significantly the invasion of microvessel compared to control implants and to 20 ng FGF-2 ± CuSO4
  • Vascular infiltration was also significantly improved by combination of CuSO4 with FGF-2, compared to FGF-2 alone (0.2 and 1 microg)
  • CuSO4 alone x 1 µg of FGF-2 combined with CuSO4
    • Jenom kombinace měla efekt
  • Collagen fiber deposition was enhanced following the combinatory loading in comparison to that with FGF-2 alone but not with CuSO4 only
  • copper associated with growth factors
    • May have synergistic effects
  • www.sciencedirect.com/science/article/abs/pii/S0142961209010849

Drynaria fortunei - Drynárije štastná

  • Promoted Angiogenesis
    • Associated With Modified MMP-2/TIMP-2 Balance and Activation of VEGF Ligand/Receptors Expression
  • Five major compounds from the water extract of D. fortunei:
    • Protocatechuic acid,
    • Caffeic acid
    • 4-O-ß-D-glucopyranoside,
    • 5,7-dihydroxychromone-7-O-rutinoside,
    • Neoeriocitrin,
    • Naringin
  • D. fortunei was confirmed to activate in vivo angiogenesis by CAM and DIVVA assays
  • D. fortunei further exhibited in vitro angiogenic effects associated with cell migration
  • Scratch wound healing assay
  • Extracellular MMP-2 activity was found to be dose-dependently augmented both in vitro and in vivo by D. fortunei.
  • MRNA and protein expressions of MMP-2, and MMP-14 were increased
  • Tissue inhibitor metalloproteinase-2 (TIMP-2), and reversion-inducing cysteine-rich protein with kazal motifs (RECK) were both decreased.
  • D. fortunei activated the gene and protein expressions of VEGF-A, -B, and VEGFR-2, -3
  • www.researchgate.net/publication/327796415_Drynaria_fortunei_Promoted_Angiogenesis_Associated_With_Modified_MMP-2TIMP-2_Balance_and_Activation_of_VEGF_LigandReceptors_Expression

Electrical, photoacoustic, piezoelectric, magnetic, and/or optical properties

Electrical stimulation (ES)

  • Promotes angiogenesis in a variety of tissues and cell types
  • The pro-angiogenic proteins VEGF and MCP-1 were significantly increased following ES compared to controls, while the anti-angiogenic factor Serpin E1/PAI-1 was significantly decreased
  • Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors
  • EFs as low as 75-100 mV mm–1 (1.5-2.0 mV across an endothelial cell)
    • Directed the reorientation, elongation and migration of endothelial cells in culture
  • Created at the endothelial cell wall by the flow of blood in both the aorta and vena cava
  • Range from 100 mV to 400 mV (Sawyer et al., 1966)
  • Injured and ischemic tissue also becomes electrically polarized
    • Extracellular K+ ions in the damaged areas
    • Leads to a flow of injury current, intracellularly through junctionally coupled cells, with an extracellular return loop
    • Thought to be involved in arrhythmogenesis (Coronel et al., 1991)
    • In diastole, damaged extracellular areas become negative relative to undamaged areas - reversed in systole
      • Currents become more diffuse and are around one-third of their diastolic magnitude (Kleber et al., 1978)
  • Extracellular injury currents, which create directly measured DC EFs of 58 mV cm–1
    • Extend over about 8 mm at the boundary between ischemic and normal tissue (Coronel et al., 1991)
    • EFs are widespread where new vessels sprout in vivo
      • There is no evidence for a direct role for EFs in angiogenesis.
  • Physiological EFs with the above parameters are applied to cells in culture to mimic the in vivo situation
    • Exert profound effects
  • Strikingly direct the orientation, the migration and the axis of division of corneal epithelial cells, for example (Nuccitelli, 1992; McCaig and Zhao, 1997; Song et al., 2002; Robinson, 1985; Zhao et al., 1999b; Zhao et al., 2002a; Zhao et al., 2002b)
  • Electrically directed cell behaviors are crucial to tissue growth and repair in development and wound healing (Nuccitelli, 1992; McCaig and Zhao, 1997; Robinson, 1985)
    • During angiogenesis
  • A small, physiological EF as low as 75-100 mV mm–1
    • Stimulated cell elongation
    • Reoriented and directed alignment of single cells and cell monolayers
    • Directed cell migration
  • Caused by induced release of VEGF from endothelial cells and required the activation of VEGF receptors (VEGFRs) and of phosphatidylinositol-3-kinase (PI3K)-Akt and Rho-ROCK elements of the VEGFR signaling pathway
  • Close association of angiogenesis with EFs in vivo and the effect of EFs on pre-angiogenic responses of endothelial cells through one of the most important VEGFR signaling pathways suggest that EFs might play an important role in angiogenesis in vivo.
  • In HUVECs is 75-100 mV mm–1
  • Experimentally measured electric fields near the cuts are 40 mV mm–1 and 100-200 mV mm–1 in bovine cornea and guinea-pig skin (Chiang et al., 1992; Barker et al., 1982)
  • Field strength will decrease exponentially within the extracellular space back from the wound
    • Edge, is 200 mV mm–1
  • journals.biologists.com/jcs/article/117/3/397/27967/Electrical-stimulation-directly-induces-pre
  • In a mouse ischemic hindlimb model, ES generated by a solar cell and applied to the ischemic region
    • Promoted migration of MSCs toward the ischemic site and upregulated expression of angiogenic paracrine factors
      • Vascular endothelial, basic fibroblast, and hepatocyte growth factors; and stromal cell-derived factor-1alpha
  • Solar cell-generated ES promoted the formation of capillaries and arterioles at the ischemic region
    • Attenuated muscle necrosis and fibrosis,
    • Prevented loss of the ischemic limb
  • Solar cell ES therapy
    • Showed higher angiogenic efficacy than conventional MSC therapy.

EphrinA1

  • Stimulated proliferation, migration, tube formation and Ca2+ flux in HUVEC and HRMVEC, and angiogenesis in rat aortic rings, with a maximum effect comparable to VEGF. EphrinA1 also induced EphA2 and VEGFR2 phosphorylation, however, VEGF did not induce EphA2 phosphorylation
  • iovs.arvojournals.org/article.aspx?articleid=2150580

FGFs, HGF, PDGF and placental growth factor (PlGF)

  • Injection of these cytokines to ischemic tissue or blood vessels increased perfusion and vascular density.
  • Extremely expensive (especially for human body mass)
  • Half-life of most cytokines was too low to render potent effects

Recombinant human bFGF


Fenofibrate

  • PPAR alpha Agonist
  • Stimulated Angiogenesis by Improving Endothelial Precursor Cell Function Via a NLRP3 Inflammasome Pathway
  • Compared with the untreated diabetic mice, wound closure and capillary densities were significantly increased in fenofibrate treated group.
  • Fenofibrate treatment restored EPC function, increased NO production, and decreased O2- level in EPCs of diabetic mice
  • Fenofibrate deregulated the activity of NLRP3 inflammasome by reducing TXNIP, NLRP3 and caspase-1 expression in EPCs of diabetic mice.
  • In vitro, fenofibrate prevented high glucose induced EPC dysfunction, deregulated NLRP3 inflammasome activity.
  • Fenofibrate inhibited IL-1beta expression caused by combination use of high glucose and lipopolysaccharide
  • Fenofibrate can accelerate wound healing in diabetic mice
    • At least in part was mediated by improving the impaired EPC function via a NLRP3 inflammasome pathway
  • www.karger.com/Article/Fulltext/479999

Ločidlo, čertovo lejna (Ferula assa-foetida)

  • Připravuje se z ní koření asa foetida
    • V perské a indické kuchyni
    • Ve vegetariánských pokrmech nahrazuje česnek a cibuli.[7]
  • Ločidlo galbanové (Ferula gummosa či Ferula galbaniflua)
    • Slouží k přípravě esenciálního oleje galbanum
      • V lékařství a kosmetice
  • Ze sušeného kořene ločidla Ferula hermonis
    • se připravuje afrodisiakum zallouh
      • Známé zejména v oblasti Blízkého východu
  • Ločidlo perské (Ferula persica) slouží k přípravě
    • Antikonvulziv,
    • Expektorant
    • Abortiv.
  • Ferula tingitana
    • Poskytuje pryskyřici, z níž se připravují léky proti zánětům průdušek, astma či chronickému nachlazení
  • cs.wikipedia.org/wiki/Lo%C4%8Didlo

Ferulic acid - 4-hydroxy-3-methoxycinnamic acid

  • A. sinensis = andělika čínská
  • Cimicifuga heracleifolia = ploštičník
  • Ligusticum chuangxiong = Koprníček
  • Spinach = špenát
  • Parsley = petržel
  • Cooked sweet corn = vařená sladká kukuřice
  • Rice bran oil = rýžový olej
  • Ferula foetida = Ločidlo čertovo lejno (Ferula assa-foetida)
  • Promoted angiogenesis in a CAM model
  • Activated angiogenesis in a HUVEC model via enhancing the expression of HIF1alpha/VEGF, PDGF
  • Inhibitors of ERK1/2 and PI3K could decrease this angiogenesis
    • By blocking of HIF1alpha and activation VEGF, PDGF
      • MAPK and PI3K signaling pathways were involved
  • [Zhou]
  • Další zdroje: Ferulic acid (mg/0.1 kg)
  • Sugar-beet pulp 800 - cukrová řepa
  • Popcorn 313 - popkorn
  • Bamboo shoots 243.6 -babusové výhonky
  • Whole grain rye bread 54 - celozrnný žitný chléb
  • Whole grain oat flakes 25–52 - ovesné vločky
  • Sweet corn 42 - sladká kukuřice
  • Pickled red beet 39 - červená řepa
  • Water dropwort 7.3–34 - halucha vodní / haluchovka vodná
  • Eggplant 7.3–35 - lilek
  • Redbeet 25 - červená řepa
  • Rice, brown, long grain parboiled 24 - rýže hnědá
  • Boiled spaghetti 13.6 - vařené špagety
  • Pasta 12 - těstoviny
  • Banana 5.4 - banán
  • Ferula communis - fenykl obří
  • Angiogenic activity of FA via stimulation of the VEGF, PDGF and HIF-1alpha pathways has been done
  • Concluded that the angiogenic effects of FA occur via two pathways which are called as PI3K and MAPK pathway
  • FA is a new potential therapeutic agent for ischemic diseases
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC5466124/
  • U obilovin se kyselina ferulová vyskytuje v otrubách
  • V pšenici vázaná na nerozpustné sloučeniny
  • Ve lněných semenech (4,1±0,2 g/kg)
  • Prokázána v zrnech ječmene
    • Kyselina ferulová patří k nejčastěji se vyskytujícím fenolickým kyselinám v ječmeni.
  • V čaji z listu jakonu (Smallanthus sonchifolius)
    • Rostliny pěstované v severních a středních Andách
  • Fazole
  • V semenech rostliny Macrotyloma uniflorum.
  • Andělika čínská (Angelica sinensis)
  • Cimicifuga heracleifolia
  • Ligusticum chuangxiong
  • V čaji zeměžluči hořké (Centaurium erythraea)
  • Luštěniny, odrůda bílé fazole námořnická fazole je nejbohatším zdrojem kyseliny ferulové mezi fazolemi obecnými (Phaseolus vulgaris)
  • Koňské gramy (Macrotyloma uniflorum)
  • Vařené sladká kukuřice uvolňuje zvýšené hladiny kyseliny ferulové
  • V oleji z rýžových otrub
  • Žitný chléb obsahuje dehydrodimery kyseliny ferulové
  • cs.vvikipedla.com/wiki/Ferulic_acid
  • Hard wheat, whole grain flour - 72.21 mg/100 g FW
  • Chocolate, dark - 24.00 mg/100 g FW
  • Date, dried - 11.83 mg/100 g FW
  • Pomegranate, pure juice - 5.38e-04 mg/100 ml
  • Marjoram, dried - 7.10 mg/100 g FW

Fucoidan, genistein, globular adiponectin


Ginseng

  • Pro-angiogenic properties in vivo models [Zhou]

P. ginseng

Ginsenosides Rg1 and Re

  • In vitro and in vivo pro-angiogenic effects
  • [Zhou]
  • Ginsenosides Rb1 and Rg1
    • Most abundant ginsenosides present in ginseng roots

Panax notoginseng

  • Pro-angiogenic properties in vivo models [Zhou]
  • Saponins from flower buds
  • Ameliorated acute myocardial infarction through pro-angiogenic and anti-apoptotic properties [Zhou]

Panax ginseng and P. notoginseng

  • Saponins isolated proved to have pro-angiogenic activities [Zhou]

Pseudo-ginseng

  • Pro-angiogenic properties in vivo models [Zhou]

Glycine

  • Vascular endothelial growth factor signaling requires glycine to promote angiogenesis
  • [ Dongqing Guo, Colin E. Murdoch, Hao Xu, Hui Shi, Dayue Darrel Duan, Asif Ahmed & Yuchun Gu]
  • Peripheral vascular occlusive disease (PVOD)
    • Common manifestation of atherosclerosis
    • High rate of morbidity
  • VEGF induces angiogenesis and can potentially be used to treat ischemic diseases
  • In clinical trials VEGF has not fulfilled its full potential with side effects
  • Glycine
    • Significantly promoted angiogenesis
    • Both in vitro and in vivo
    • Effectively protected mitochondrial function
  • Activation of glycine transporter 1(GlyT1)
    • Induced by VEGF
    • Led to an increase in intracellular glycine
  • Glycine
    • Directly bounded to voltage dependent anion channel 1 (VDAC1) on the mitochondrial outer membrane
    • Inhibited its opening
    • Glycine as a necessary mediator in VEGF signalling
      • Via the GlyT1-glycine-mTOR-VDAC1 axis pathway
  • www.nature.com/articles/s41598-017-15246-3
  • VEGF is a key regulator of angiogenesis
    • Specific mitogen for endothelial cells
  • Three key pathways in the VEGF signals have been reported:
    • Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-MAPK (mitogen-activated protein kinase) pathway
    • PI3K (phosphatidylinositol 3-kinase)-Akt pathway
    • Src-FAK (focal adhesion kinase) pathway
  • Transcriptional coactivator PGC-1 alpha (peroxisome-proliferator-activated receptor-gamma coactivator-1 alpha)
    • A potent metabolic sensor and regulator
    • Induced by a lack of nutrients and oxygen
    • Powerfully regulates in vivo VEGF expression and angiogenesis in cultured muscle cells and skeletal muscle
  • Mammalian target of rapamycin complex 2 (mTORC2)-fork head box protein O1 (FoxO1) axis in VEGF signal
    • Feedback activation of receptor tyrosine kinases
  • VEGF is known to cause vasodilation
    • Increase vascular permeability
      • Contribute to the pathophysiological processes related to VEGF over-activity
  • Amino acids have been identified as potential candidates in promoting survival
  • Key mediators involved in VEGF signaling
    • Glycine is required in the VEGF signaling pathways
    • Glycine could promote the mitochondrial function by inhibiting VDAC1 opening.
  • VEGF induces phosphorylation of the well characterised ribosomal S6 protein
    • Has no effect on mTOR expression
  • Removal of all amino acids in the cell medium
    • Resulted in loss of VEGF-induced ECs proliferation
      • With no change of the expression of P-S6 in response to VEGF
  • Unique role for amino acids in the mTOR signaling induced by VEGF
  • Glycine was required in the VEGF signals
  • Intracellular content of alanine(Ala), arginine(Arg), asparagine(Asn), aspartic acid(Asp), cysteine(Cys), ?-aminobutyric acid(Gaba), glutamine(Gln), glutamic acid(Glu), glycine(Gly), histidine (His), isoleucine(Ile), leucine(Leu), lysine 37, methionine(Met), phenylalanine(Phe), proline(Pro), serine(Ser), threonine(Thr), tryptophan(Trp), tyrosine(Tyr) and valine(Val) in control and 20 ng/ml VEGF-treated ECs for 24 h
  • Glycine was higher in ECs cytoplasm induced by VEGF
  • Exogenous glycine obviously elevated the level of P-S6 via the mTOR signaling pathway
    • But had no effect on S6 expression
    • Other amino acids also have the same effects
  • During the hind limb ischemia surgery
    • Glycine was administered into the saphenous artery
    • Immediately tied off prior to a 1.5 mm section being removed
  • Control mice were treated with same volume of saline
  • Continuous administration of glycine through dietary supplementation after ischemia
    • During the two-week period.
  • Glycine treatment enhanced neovascularization significantly
    • Promoting the recovery of vascular flow from the third day
  • Glycine promoted HUVECs to form networks in vitro
  • Glycine alone promoted the angiogenesis on the chorioallantoic membrane
  • Glycine obviously promoted the mitochondrial function
  • Glycine induced increase of oxygen consumption (OCR) coupled to FCCP
  • mitochondrial activity also significantly increased with the stimulation of glycine
  • Intracellular ATP production increased for nearly 100% in glycine-induced ECs
  • Mitochondrial membrane potential (??m) is essential to maintain mitochondrial oxidative phosphorylation
    • Produces the adenosine triphosphate
    • Maintains the normal physiological function of cells
  • Glycine alone decreased the intracellular ROS production
  • VEGF activated GlyT1 and glycine directly bound to VDAC1 on the mitochondria
  • Glycine consumption and expression of the mitochondrial glycine biosynthetic pathway
    • Were strongly correlated with the proliferation rate of cancer cells
  • Defects in glycine metabolism in the mitochondria as a result of reduction in mitochondrial
    • Serine hydroxymethyltransferase (SHMT2)
    • Glycine C-acetyltransferase (GCAT) expression
  • Are partly responsible for the reduction in mitochondrial translation
  • Sarcosine
    • The inhibitor of glycine transporter (GlyT)
    • Could inhibit the proliferation induced by VEGF
  • Two kinds of glycine transporters including GlyT1 and GlyT222
  • VEGF could promote the expression of GlyT1
  • Knocking down the expression of GlyT1 using siRNA by electroporation
    • VEGF couldn’t increase the intracellular glycine with siGlyT1 treatment
  • VEGF activated the glycine transporter 1 and increased the intracellular glycine.
    • Glycine significantly inhibited the VDAC-1 currents
  • VEGF activated GlyT1 and glycine directly bound to VDAC-1 on the mitochondria outer membrane
  • Endothelial cells rely on glycolysis rather than via oxidative phosphorylation
  • Enhanced mitochondrial function was mediated by activating
    • MTOR signaling pathway
    • Effects relied on the presence of glycine
  • Glycine showed increasing in intracellular pools by the stimulation of VEGF
  • Glycine (Gly) is the simplest non-essential amino acid
  • Participates in the synthesis of proteins and many physiologically important functions, including
    • Anti-inflammation
    • Immunomodulation
    • Cytoprotection
    • Neurotransmitter
  • Glycine has been showed to be related to the rapid cancer cell proliferation
  • Could reverse the expression of aging phenotypes
  • Administration of glycine reduced mild ischemia-reperfusion injury in the kidney in vivo
    • Decreasing initial damage
    • Preventing chronic hypoxia
  • Glycine could mimic the effects of VEGF on ECs to promote
    • In vitro matrigel angiogenesis
    • In vivo angiogenesis
      • Chorioallantoic membrane
      • Hind-limb ischemia
  • Effectively protected the mitochondrial functions of ECs
  • Glycine could directly bind to VDAC1 and inhibit the opening of VDAC1
  • 3 subtypes of VDAC
    • VDAC1 is highly expressed in human
      • Controls the transit of adenine nucleotides, Ca2+, and other metabolites both into and out of the mitochondria
      • May be also a constituent of the mitochondrial permeability transition pore (PTP)
      • Major role in mitochondria mediated apoptosis
  • Down regulation of VDAC-1 by siRNA
    • Prevents cisplatin induced Bax activation and cell death
  • Simplest stable amino acid (carbamic acid is unstable),
  • NH2-CH2-COOH
  • One of the proteinogenic amino acids
  • Encoded by all the codons starting with GG (GGU, GGC, GGA, GGG)
  • Glycine is integral to the formation of alpha-helices
  • Most abundant amino acid in collagen triple-helices
  • Glycine is also an inhibitory neurotransmitter
  • Interference with its release within the spinal cord (such as during a Clostridium tetani infection)
    • Can cause spastic paralysis due to uninhibited muscle contraction.
  • Glycine is a colorless, sweet-tasting crystalline solid.
  • The only achiral proteinogenic amino acid.
  • Can fit into hydrophilic or hydrophobic environments
    • Minimal side chain of only one hydrogen atom.
  • Acyl radical is glycyl.
  • en.wikipedia.org/wiki/Glycine
  • Glycine functions as a bidentate ligand for many metal ions.
    • Typical complex is
      • Cu(glycinate)2
      • Cu(H2NCH2CO2)2
    • Exists both in cis and trans isomers.
  • Glycine reacts with many reagents
    • N-centered
    • Carboxylate-center
  • Glycine condenses with itself to give peptides, beginning with the formation of glycylglycine
  • Pyrolysis of glycine or glycylglycine gives 2,5-diketopiperazine, the cyclic diamide.
  • en.wikipedia.org/wiki/Glycine
  • Glycine is not essential to the human diet
    • Is biosynthesized in the body from the amino acid serine
      • Derived from 3-phosphoglycerate
  • Metabolic capacity for glycine biosynthesis
    • Does not satisfy the need for collagen synthesis
  • Enzyme serine hydroxymethyltransferase
    • Catalyses this transformation via the cofactor pyridoxal phosphate
      • serine + tetrahydrofolate = glycine + N5,N10-Methylene tetrahydrofolate + H2O
  • In the liver of vertebrates
    • Glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme)
      • Conversion is readily reversible:
        • CO2 + NH+ 4 + N5,N10-Methylene tetrahydrofolate + NADH + H+ = Glycine + tetrahydrofolate + NAD+
  • Glycine can also be derived from.
    • Threonine
    • Choline
    • Hydroxyproline
  • Via inter-organ metabolism of the liver and kidneys

Glycine is degraded via three pathways

  • Predominant pathway in animals and plants
    • Reverse of the glycine synthase pathway mentioned above = glycine cleavage system
      • Glycine + tetrahydrofolate + NAD+ = CO2 + NH4+ + N5,N10-Methylene tetrahydrofolate + NADH + H+
  • Second pathway
    • Reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase
    • Serine is then converted to pyruvate by serine dehydratase
  • Third pathway of its degradation
    • Glycine is converted to glyoxylate by D-amino acid oxidase
    • Glyoxylate is then oxidized by hepatic lactate dehydrogenase to oxalate in an NAD+-dependent reaction
  • Half-life of glycine and its elimination from the body
    • Varies significantly based on dose
    • Varied between 0.5 - 4.0 hours
  • Glycine is extremely sensitive to antibiotics which target folate
    • Blood Glycine levels drop severely within a minute of antibiotic injections
    • Some antibiotics can deplete more than 90% of Glycine within a few minutes of being administered
  • Glycine is as a precursor to proteins
    • Most proteins incorporate only small quantities of glycine
    • Notable exception being collagen - about 35% glycine
      • Periodically repeated role in the formation of collagen's helix structure in conjunction with hydroxyproline
  • Delta-aminolevulinic acid
    • Key precursor to porphyrins
    • Biosynthesized from glycine and succinyl-CoA by the enzyme ALA synthase
  • Glycine provides the central C2N subunit of all purines
  • Glycine is an inhibitory neurotransmitter in the central nervous system
    • Especially in the spinal cord, brainstem, and retina
  • When glycine receptors are activated,
    • Chloride enters the neuron via ionotropic receptors
      • Causing an inhibitory postsynaptic potential (IPSP)
  • Strychnine is a strong antagonist at ionotropic glycine receptors
  • Bicuculline is a weak one
  • Glycine is a required co-agonist along with glutamate for NMDA receptors
    • This behaviour is facilitated at the (NMDA) glutamatergic receptors which are excitatory
  • LD50 of glycine is 7930 mg/kg in rats (oral)
    • Usually causes death by hyperexcitability
  • Glycine is not widely used in foods for its nutritional value, except in infusions.
  • Glycine's role in food chemistry is as
    • Flavorant mildly sweet
    • Counters the aftertaste of saccharine
    • Preservative properties - complexation to metal ions
  • Metal glycinate complexes, e.g. copper(II) glycinate are used as supplements for animal feeds
  • Glycine is an intermediate in the synthesis of a variety of chemical products.
    • Manufacture of the herbicides
      • Glyphosate
      • Iprodione
      • Glyphosine
      • Imiprothrin
      • Eglinazine
  • Intermediate of the medicine such as thiamphenicol
  • Significant component of some solutions used in the SDS-PAGE method of protein analysis
  • Buffering agent,
  • Maintaining pH
  • Preventing sample damage during electrophoresis
  • To remove protein-labeling antibodies from Western blot membranes - as stripping.
  • Glycine outside the earth was confirmed in 2009
    • Samples that had been taken in 2004 by the NASA spacecraft Stardust from comet Wild 2 and subsequently returned to earth
    • In the Murchison meteorite in 1970
    • Cometary glycine bolstered the theory of panspermia
      • "building blocks" of life are widespread throughout the Universe
    • 2016, detection of glycine within Comet 67P/Churyumov-Gerasimenko by the Rosetta spacecraft
  • Glycine outside the solar system in the interstellar medium has been debated
  • 2008, the Max Planck Institute for Radio Astronomy
    • Spectral lines of a glycine-like molecule aminoacetonitrile in the Large Molecule Heimat
      • A giant gas cloud near the galactic center in the constellation Sagittarius
  • Glycine belongs to a group of amino acids that constituted the early genetic code
    • Low complexity regions (in proteins), that may resemble the proto-peptides of the early genetic code
      • Are highly enriched in glycine

Presence in foods - food g/100g

  • Snacks, pork skins 11.04
  • Sesame seeds flour (low fat) 3.43
  • Beverages, protein powder (soy-based) 2.37
  • Seeds, safflower seed meal, partially defatted 2.22
  • Meat, bison, beef and others (various parts) 1.5-2.0
  • Gelatin desserts 1.96
  • Seeds, pumpkin and squash seed kernels 1.82
  • Turkey, all classes, back, meat and skin 1.79
  • Chicken, broilers or fryers, meat and skin 1.74
  • Pork, ground, 96% lean / 4% fat, cooked, crumbles 1.71
  • Bacon and beef sticks 1.64
  • Peanuts 1.63
  • Crustaceans, spiny lobster 1.59
  • Spices, mustard seed, ground 1.59
  • Salami 1.55
  • Nuts, butternuts, dried 1.51
  • Fish, salmon, pink, canned, drained solids 1.42
  • Almonds 1.42
  • Fish, mackerel 0.93
  • Cereals ready-to-eat, granola, homemade 0.81
  • Leeks, (bulb and lower-leaf portion), freeze-dried 0.7
  • Cheese, parmesan (and others), grated 0.56
  • Soybeans, green, cooked, boiled, drained, without salt 0.51
  • Bread, protein (includes gluten) 0.47
  • Egg, whole, cooked, fried 0.47
  • Beans, white, mature seeds, cooked, boiled, with salt 0.38
  • Lentils, mature seeds, cooked, boiled, with salt 0.37
  • en.wikipedia.org/wiki/Glycine

Látky uvolňujicí H2S

  • Přímo stimuluje VEGF2
  • částečně imitace buněčné hypoxie (blokuje Fe na cytochromech oxidační fosforylace)

Induce angiogenesis:

  • Epidermal growth factor receptors (ErbB1 and ErbB2),
  • Insulin like growth factor-I receptor (IGF-IR)
  • Hepatocyte growth factors
  • Platelet-derived growth factors (PDGF)
  • Cyclooxygenases (COX)

L-Arginine Supplementation - CAVE - JEN KRATKODOBE, ideálně + stim. BH4

  • Pursued as a potential approach to restoring NOS-mediated NO production in patients with cardiovascular disease
  • Completed clinical trials have largely failed to show beneficial effects
  • In some cases demonstrated evidence of harm
    • 3 g of L-arginine per day delivered orally for 6 months resulted in
      • Impaired flow-mediated vasodilation
      • Reduced vascular compliance
      • Low plasma and urinary nitrites and nitrates in a cohort study of patients with peripheral arterial disease
  • Patients receiving L-arginine
    • Scored lower on treadmill assessments of exercise capacity compared to placebo-treated
  • 3 g of L-arginine three times daily for 6 months
    • Failed to produce a significant effect on ejection fraction or vascular stiffness after myocardial infarction
  • L-arginine treatment
    • Exhibit a higher death rate than the control group leading to closure of enrollment due to safety concerns
  • Supplementation of L-arginine under conditions of BH4 depletion
    • Is not only insufficient to recouple NOS
    • But in fact exacerbates NOS uncoupling
  • Administration of L-arginine alone would not be expected to improve endothelial function in disease states characterized by BH4 depletion
  • link.springer.com/article/10.1007/s11897-012-0097-5

Inhibice L-N-monomethylarginine (L-NMMA)


NO-enhancing drugs

  • Nitroglycerin,
  • Molsidomine,
  • Minoxidil,
  • PDE5 inhibitors

Uvolnění NO a vazodilatace

  • Je součástí stinálů angiogeneze

Stimulace NOS + tetrahydrobiopterin (kofaktor NOS)

Arginin - donor NO

Shear stres cévní stěny

  • Tření cévy/tkáně
  • Vyšším průtokem krve při vazodilataci
  • Teplo
    • Infrakomory
    • Sauny
  • Podtlakové nasávání krve
    • Vakupress
    • Baňkování
  • Polohy hlavou dolů
  • Spaní
    • Na zádech bez polštáře na rovné ploše
    • Na šikmé ploše s hlavou o něco níže než nohy
    • Poseldní jidlo max. 3h před spaním - aby hlavní proud krve šel do mozku aj. a ne do žaludku a střev
  • Ultravzukové dráždění
  • Možná magnetoterapie (spíše usnadní vnikání živin do hypoxické tkáně)

Reakce na hypoxii (CO2)

  • Karboxyterapie - plynové injekce CO2
  • řízená hypoxie v podtlakové komoře
  • Dechová cvičení se zařazením výdrže nedýchat, krátké sekvence dýchání do pytlíku

Lékové donory NO

  • Nitromint spray pod jazyk /na místo s nedokrvením
  • Trinitroglycerinové tabletky (na aginu pectoris) pod jazyk
  • Proti vyčerpání efektu po pár dávkách je potřeba dodat prekurzory glutathionu (-SH donory) - třeba N-acetylcystein

Omega-6 nenasycené mastné kyseliny

  • Světlicový olej / bodlákový olej

Orally administrated bFGF

  • Heal gastric ulcers caused by nonsteroidal anti-inflammatory drugs
  • AFGF induced angiogenesis in the ulcer bed and accelerated the healing of ulcers in animals

A phase I clinical trial of therapeutic angiogenesis using bFGF protein in heparin-alginate

  • Slow-release microcapsules in 8 patients
    • In symptomatic, severe coronary artery disease that was not amenable to complete revascularization by either percutaneous transluminal coronary angioplasty or coronary artery bypass grafting
  • Demonstrated the feasibility and safety of bFGF administration for coronary artery diseases
  • Angiogenic and other growth factors can heal
    • Gastrointestinal ulceration
    • Coronary artery diseases
  • Antiulcer drug sucralfate (sucrose aluminum sulfate or Carafate)
    • Appears to act by protecting endogenous mucosal bFGF from degradation by acid.
  • www.hindawi.com/journals/mi/2013/127170/

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha; encoded by the gene PPARGC1A)

  • Master regulators of mitochondrial biogenesis and oxidative metabolism
  • VEGF has been shown to activate PGC-1a
  • Increased mitochondrial biogenesis in endothelial and other cell types (Arany et al., 2008; Wright et al., 2008)
  • PGC-1alpha expression in heart and muscle cells
    • Induces angiogenesis,
      • Implying that PGC-1alpha stimulates vascularization and prepares ischemic tissues for oxidative metabolism that is permitted by improved oxygenation
  • Induction of PGC-1alpha in endothelial cells by high levels of glucose
    • Mediates cellular dysfunction and impairs angiogenesis (Sawada et al., 2014)
  • journals.biologists.com/jcs/article/127/20/4331/54727/Angiogenesis-revisited-role-and-therapeutic

Activation of PPARalpha and PPARgamma

  • Leads to endothelial tube formation in an endothelial/interstitial cell co-culture assay
  • Associated with increased production of the angiogenic cytokine vascular endothelial growth factor (VEGF)
  • Neovascularization also occurs in vivo
    • PPARalpha and PPARgamma agonists are used in the murine corneal angiogenic model
    • PPARalpha knockout mice and mice treated with a specific PPARgamma inhibitor
      • Angiogenic response is PPAR mediated
  • PPARalpha- and PPARgamma-induced angiogenesis is associated with local VEGF production
  • PPARalpha and PPARgamma agonists, there is increased phosphorylation of endothelial nitric oxide synthase and Akt.
  • diabetes.diabetesjournals.org/content/57/5/1394

Pouteria lucuma oil

  • Wound-healing acceleration and closure
    • Linoleic acid,
    • Oleic acid,
    • Palmitic acid,
    • Stearic acid
    • Gamma-linolenic acid
  • [Zhou]


Proliferin (PLF)

  • Stimulated angiogenesis
  • Proliferin-related protein (PRP) inhibited anigogenesis
  • Mouse placenta secretes an angiogenic activity during the middle of pregnancy
    • Primarily to PLF
  • Later in gestation releases a factor that inhibits angiogenesis - PRP
  • Incubation of placental tissue with PLF
    • Led to the specific binding of this hormone to capillary endothelial cells
  • science.sciencemag.org/content/266/5190/1581

Prostaglandin E1 (PGE1)

  • Potent vasodilator and induces angiogenesis in animal tissues
  • PGE1 improves hemodynamic parameters in patients with heart failure listed for heart transplantation (HTX)
  • PGE1 could be a potent inducer of angiogenesis and the angiogenic factor VEGF
    • Could cause reduced fibrosis in the failing human heart
  • www.jhltonline.org/article/S1053-2498(00)00317-X/abstract

Puerarin

  • One of the major components of Radix Puerariae
  • Induced angiogenesis in the non-ischemic and ischemic myocardium to prevent myocardial infarction
    • Activation of VEGF, HIF1alpha, and endothelial nitric oxide synthase (eNOS)
  • Improved cardiac angiogenesis and cardiac function
    • By upregulating VEGFA, Ang1, and Ang2 in rats with myocardial infarction
  • [Zhou]
  • Kudzu extrakt (puerarin ?60%) - použití
  • Příklad užití volně sypaného extraktu:
    • Dávkovat extrakt Kudzu (puerarin ? 60%) kávová lžička s extraktem 1x denně jako doplněk stravy , max. 2x až 3x denně.
  • Extrakt v plněných kapslích 500mg:
    • Extrakt Kudzu (puerarin ? 60%) v plněných kaplích po 500mg
    • 1 kapsli 1x denně jako doplněk stravy
    • Při zdravotních potížích 1 kapsli 2x až 3x denně
  • www.vinaturae.cz/forum/topic168-kudzu-extrakt-puerarin-60-pouziti.html
  • Puerarin je isoflavanonový glykosid
    • Z kořenů rostlin čeledi Leguminosae
    • V Číně je v současné době používán k léčbě ischemických cerebrovaskulární onemocnění a jiných vaskulární dysfunkcí (Wang et al., 2014; Zhou et al., 2014a)
  • Hlavní biologicky aktivní složkou izolovanou z kořene Pueraria lobata (Willd.) Ohwi - Gegen v tradiční čínské medicíně (Zhou et al., 2014b).
    • Použití puerarinu jako potenciálního léčiva Alzheimerovy choroby je zdůvodňováno jeho neuroprotektivním účinkem před toxickým vlivem neurotoxického peptidu Abeta (Wang et al., 2008; Zhang et al., 2008a,b, 2010; Li et al., 2010) a skutečností, že zlepšuje mikrocirkulaci krve v mozku (Xu et al., 2005; Chang et al., 2009).
  • toxicology.cz/modules.php?name=News&file=print&sid=817
  • (Radix puerariae) notably of the kudzu plant
  • Puerarin is the 8-C-glucoside of daidzein


Radix Achyranthis Bidentatae

  • Pro-angiogenic properties in vivo models [Zhou]

Radix Angelicae Sinensis

  • Pro-angiogenic properties in vivo models [Zhou]

Radix Cyathulae

  • Pro-angiogenic properties in vivo models [Zhou]

Radix Rehmannia Glutinosa

  • Pro-angiogenic properties in vivo models [Zhou]

Radix Salviae Miltiorrhizae (danshen in Chinese)

  • Pro-angiogenic properties in vivo models [Zhou]
  • Its watersoluble fraction of salvianolic acids (SAs)
    • Pro-angiogenic properties on in vitro cultured endothelial progenitor cells (EPCs) and the CAM model

Salvianolic acid A

  • Accelerated ischemia-induced neovascularization in the ischemic rat myocardium in vivo
    • By stimulating EPCs, through VEGF, VEGFR2, and MMP9

Salvianolic acid B

  • Also improved angiogenesis by increasing the gene expression of VEGF, VEGFR2, and MMP2
  • [Zhou]

SIRT1 stimulace

  • The NAD+-dependent deacetylase activity of SIRT1 deacetylates NICD, thereby reducing the stability of NICD, and promoting vascularization (Chalkiadaki and Guarente, 2012; Guarani and Potente, 2010). SIRT1 deficiency results in stalk cell phenotypes by decreasing NICD destabilization (Potente et al., 2007). Similarly, SIRT1 regulates vessel branching by deacetylating FOXO1, a transcription factor that inhibits endothelial angiogenic activity (Eijkelenboom and Burgering, 2013). FOXO1 deficiency causes abnormal vascular branching that leads to embryonic lethality, demonstrating that metabolic signals can intricately regulate vascular branching (Furuyama et al., 2004; Oellerich and Potente, 2012).
  • journals.biologists.com/jcs/article/127/20/4331/54727/Angiogenesis-revisited-role-and-therapeutic

Sauna

  • I při léčbě řady onemocnění, která jsou vyvolána nedostatkem kofaktoru tetrahydrobiopterinu (BH4)
  • Sauna může zvýšit použitelnost BH4 tím, že přímo zvyšuje tvorbu speciálního proteinu HSP (heat shock protein), který se v těle produkuje jako reakce na teplotní šok
  • HSP se vytváří v sauně jako reakce na teplo a zabraňuje odbourávání důležitého proteinu, který se podílí na tvorbě kofaktoru BH4.
  • Z toho vyplývající zvýšení BH4 zároveň zvyšuje tvorbu oxidu dusnatého (NO), což rozšiřuje cévy.
  • kulturistika.ronnie.cz/c-26023-sauna-podporuje-svalovy-rust-a-zotaveni.html

Statins (?)

  • May depend in part on their ability to increase BH4 bioavailability
    • Demonstrated both in vitro and in patients

Ascorbic acid and 5-methyl-tetrahydrofolate


Syntenin - syndecan-binding protein, SDCBP

  • Syntenin knockdown in human umbilical vein endothelial cells (HUVECs)
    • Impaired vascular endothelial growth factor (VEGF)-mediated proliferation, migration, invasion, vascular permeability, and nitric oxide (NO) production.
    • Suppressed expression of the VEGFR2 target genes VEGF, MMP2, and Nurr77 as well as VEGF-induced angiogenesis in vitro and in vivo
    • Decreased cell-surface levels of ephrin-B2
  • Syntenin exists in complex with VEGFR2 and ephrin-B2
  • Syntenin promotes VEGF signaling
    • Its PDZ-dependent interaction with ephrin-B2
    • Enhances VEGF-mediated VEGFR2 endocytosis
      • Subsequent downstream signaling and angiogenesis in endothelial cells
  • Syntenin appears necessary for VEGF-induced angiogenesis and VEGFR2 signaling
    • By enhancing the cell surface expression of ephrin-B2
      • Thereby the interaction between VEGFR2 and ephrin-B2 to induce VEGFR2 endocytosis and signaling
  • Lipid raft membrane microdomains
    • Regulate cell communication by compartmentalizing signal transduction proteins within lipid microdomains
  • Localization of VEGFR2 to lipid rafts
    • Facilitates its dimerization and endocytosis in ECs
      • Steps required for VEGF-mediated signaling
  • Syntenin localized to lipid rafts in HUVECs
    • Colocalization of syntenin with the well-known lipid raft marker, flotillin-1
  • Loss of syntenin could decrease ephrin-B2-mediated VEGFR2 endocytosis and subsequent VEGFR2 signaling and angiogenesis
  • Loss of flotillin-1 leads to a reduction in the level of ephrin-B2 protein
    • Reduction is rescued by treatment with MG132
  • www.oncotarget.com/article/16452/text/

Tetrahydrobiopterin


VESSEL DUE F tobolky - sulodexidsulodexidum

  • Zlepšení prokrvení a novotovorby cév, Rp.
  • Stimulační protizánětlivé účinky mají význam při udržování integrity a reparativních schopností endotelu a cévní stěny. Jedná se o zvýšení aktivity superoxiddismutázy, hepatocytárního a fibroblastového růstového faktoru nebo o stimulaci exprese heparan sulfátu na buněčných površích. Významným supresivním protizánětlivým účinkem je např.
    • Snížení uvolňování kyslíkových radikálů, které hrají důležitou roli při spouštění zánětlivé reakce u diabetu a poškození endotelu,
    • Inhibice aktivity heparanázy v glomerulech
    • Snížení exprese matrix-metaloproteinázy 9 (MMP-9)
    • Snížení expr. faktoru TGFß 1
    • Snížení aktivity růstového faktoru VEGF
  • Indikace:
    • Ischemická choroba srdeční,
    • Ischemická choroba dolních končetin
    • Cerebrovaskulární patologie
    • Cévní komplikace diabetu (nefro-, retino- a neuropatie)
    • žilní onemocnění provázené trombózou s poškozením chlopní
      • Chronická žilní insuficience,
      • Bércové vředy
      • Sekundární prevence hluboké žilní trombózy
  • www.kardiologickarevue.cz/casopisy/kardiologicka-revue/2013-4/mechanizmus-pleiotropniho-ucinku-sulodexidu-47017



Tip k prostudování a dohledání

  • Inj. GUNA MD neural, ev. v kombinaci s B12
  • Citikolin a Rischiaril
    • Pamatuji si toto z přednášek italských profesorů , kteří těmto látkám připisují velký neuroprotektivní účinek
  • Dále bych podával C vitamin, alespoň 2 gramy denně v lipozomální formě / Lipo-C- ASkor, lépe asi začít infuzemi, dávají řádově desítky gramů denně, + cca 4000 j. vitaminu D denně.
  • Kontaktujte doktorku Lucii Kotlářovou z inPHARMU, je to nesmírně vzdělaná a pro medicinu zapálená žena-chodící vědecká encyklopedie
  • [Dr. Zahradník]

Angiogenesis activators

  • Tumour cells produce and secrete angiogenesis activators to stimulate angiogenesis
  • Basic fibroblast growth factor (bFGF)
  • Vascular endothelial growth factor (VEGF)
  • Are upregulated by
    • Glycolysis end products such as lactate and pyruvate
    • Interleukin-8 (IL-8),
    • Angiogenin (ANG)
    • Tissue inhibitors of metalloproteinase-1 (TIMP-1)
  • Inhibition by canagliflozin was confirmed
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC9738342/

Electrical, photoacoustic, piezoelectric, magnetic, and/or optical properties

  • Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors
  • EFs as low as 75-100 mV mm–1 (1.5-2.0 mV across an endothelial cell)
    • Directed the reorientation, elongation and migration of endothelial cells in culture
  • Created at the endothelial cell wall by the flow of blood in both the aorta and vena cava
  • Range from 100 mV to 400 mV (Sawyer et al., 1966)
  • Injured and ischemic tissue also becomes electrically polarized
    • Extracellular K+ ions in the damaged areas
    • Leads to a flow of injury current, intracellularly through junctionally coupled cells, with an extracellular return loop
    • Thought to be involved in arrhythmogenesis (Coronel et al., 1991)
    • In diastole, damaged extracellular areas become negative relative to undamaged areas - reversed in systole
      • Currents become more diffuse and are around one-third of their diastolic magnitude (Kleber et al., 1978)
  • Extracellular injury currents, which create directly measured DC EFs of 58 mV cm–1
    • Extend over about 8 mm at the boundary between ischemic and normal tissue (Coronel et al., 1991)
    • EFs are widespread where new vessels sprout in vivo
      • There is no evidence for a direct role for EFs in angiogenesis.
  • Physiological EFs with the above parameters are applied to cells in culture to mimic the in vivo situation
    • Exert profound effects
  • Strikingly direct the orientation, the migration and the axis of division of corneal epithelial cells, for example (Nuccitelli, 1992; McCaig and Zhao, 1997; Song et al., 2002; Robinson, 1985; Zhao et al., 1999b; Zhao et al., 2002a; Zhao et al., 2002b)
  • Electrically directed cell behaviors are crucial to tissue growth and repair in development and wound healing (Nuccitelli, 1992; McCaig and Zhao, 1997; Robinson, 1985)
    • During angiogenesis
  • A small, physiological EF as low as 75-100 mV mm–1
    • Stimulated cell elongation
    • Reoriented and directed alignment of single cells and cell monolayers
    • Directed cell migration
  • Caused by induced release of VEGF from endothelial cells and required the activation of VEGF receptors (VEGFRs) and of phosphatidylinositol-3-kinase (PI3K)-Akt and Rho-ROCK elements of the VEGFR signaling pathway
  • Close association of angiogenesis with EFs in vivo and the effect of EFs on pre-angiogenic responses of endothelial cells through one of the most important VEGFR signaling pathways suggest that EFs might play an important role in angiogenesis in vivo.
  • In HUVECs is 75-100 mV mm–1
  • Experimentally measured electric fields near the cuts are 40 mV mm–1 and 100-200 mV mm–1 in bovine cornea and guinea-pig skin (Chiang et al., 1992; Barker et al., 1982)
  • Field strength will decrease exponentially within the extracellular space back from the wound
    • Edge, is 200 mV mm–1
  • journals.biologists.com/jcs/article/117/3/397/27967/Electrical-stimulation-directly-induces-pre
  • In a mouse ischemic hindlimb model, ES generated by a solar cell and applied to the ischemic region
    • Promoted migration of MSCs toward the ischemic site and upregulated expression of angiogenic paracrine factors
      • Vascular endothelial, basic fibroblast, and hepatocyte growth factors; and stromal cell-derived factor-1alpha
  • Solar cell-generated ES promoted the formation of capillaries and arterioles at the ischemic region
    • Attenuated muscle necrosis and fibrosis,
    • Prevented loss of the ischemic limb
  • Solar cell ES therapy
    • Showed higher angiogenic efficacy than conventional MSC therapy.

Neuropilins (NRP1 and NRP2)

  • Coreceptors for the VEGF family
  • NRP1
    • Binding affinity between VEGF-A and PLGF and VEGFR2 increases (Ferrara and Adamis, 2016).
  • NRP2
    • VEGF-C, and VEGF-D have increased binding affinity with VEGFR-3

TCM 700 ŠAOLINOVÝ OLEJ 25 ml

  • Obsahuje směs pro-angiogenních bylin
  • Vhodné k masáži tkání, kde je potřeba stimulovat prokrvení a hojení
  • Ženšen nepravý - kořen (Všehoj nepravý, Pseudoginseng radix, San qi) - ano
  • Myrhovník pravý - klejopryskyřice (Myrrhae resina, Mo yao)
  • Kadidlovník pravý - klejopryskyřice (Olibanum gummi, Ru xiang) - Boswelia serrata - možná
  • Světlice barvířská - květ (Carthami tinctorii flos, Hong hua) - ano
  • Drynarie Fortunova (Drynaria fortunei, Gu si bu) - ano
  • Děhel pýřitý - kořen (Angelica pubescens, Angelicae pubescentis radix, Du huo)
  • Andělika čínská - kořen (Děhel čínský, Angelicae sinensis radix, Dang gui) - ano/ne
  • Sezam indický - semeno (Sesami indici semen, Hei zhi ma) - ano
  • Šácholan - květ (Magnoliae flos, Su xin hua) - ne
  • doplnky-stravy.heureka.cz/tcm-700-saolinovy-olej-25-ml/#specifikace

Regulace angiogeneze

  • Ischaemia/hypoxia-induced genes (HIFs)
  • Epidermal growth factor (EGF)
  • PDGF (Semenza, 2000)

Angiogenesis activators

tPA


O úroveň výše

Poslední aktualizace: 10. 12. 2023 20:35:24