ATP-Sensitive Potassium Channel Activation Induces Angiogenesis In Vitro and In Vivo

Umaru, Bukar; Pyriochou, Anastasia; Kotsikoris, Vasileios; Papapetropoulos, Andreas; Topouzis, Stavros

doi:10.1124/jpet.114.222000

Cited by 32 publications

(26 citation statements)

References 60 publications

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“…ATP-sensitive potassium channels (K ATP ), a major mediator of the effects of H 2 S, were shown to lie upstream of p38 [30]. In line with these findings, direct K ATP , channel openers also promote angiogenesis [30, 87]. …”

Section: H2s Signaling In Angiogenesis: Downstream Mediatorsmentioning

confidence: 95%

Regulation and role of endogenously produced hydrogen sulfide in angiogenesis

Katsouda

Bibli

Pyriochou

et al. 2016

Pharmacological Research

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Recent studies have implicated endogenously produced H2S in the angiogenic process. On one hand, pharmacological inhibition and silencing of the enzymes involved in H2S synthesis attenuate the angiogenic properties of endothelial cells, including proliferation, migration and tube-like structure network formation. On the other hand, enhanced production of H2S by substrate supplementation or over-expression of H2S-producing enzymes leads to enhanced angiogenic responses in cultured endothelial cells. Importantly, H2S up-regulates expression of the key angiogenic factor vascular endothelial growth factor (VEGF) and contributes to the angiogenic signaling in response to VEGF. The signaling pathways mediating H2S-induced angiogenesis include mitogen-activated protein kinases, phosphoinositide-3 kinase, nitric oxide/cGMP-regulated cascades and ATP-sensitive potassium channels. Endogenously produced H2S has also been shown to facilitate neovascularization in prototypical model systems in vivo, and to contribute to wound healing, post-ischemic angiogenesis in the heart and other tissues, as well as in tumor angiogenesis. Targeting of H2S synthesizing enzymes might offer novel therapeutic opportunities for angiogenesis-related diseases.

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Section: H2s Signaling In Angiogenesis: Downstream Mediatorsmentioning

confidence: 95%

Regulation and role of endogenously produced hydrogen sulfide in angiogenesis

Katsouda

Bibli

Pyriochou

et al. 2016

Pharmacological Research

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“…Interestingly, in our study, potassium channel blockers were also enriched in PhenoCluster 4. Modulation of potassium channel activity has been shown to influence endothelial cell functions, including angiogenesis (Brähler et al, 2009;Umaru et al, 2015). Thus, we speculate that the in vitro angiogenic effect of glutamate receptor inhibition is mediated by the changes of potassium transit via the glutamateactivated potassium channels.…”

Section: Discussionmentioning

confidence: 82%

Multi-Parametric Profiling of Endothelial Cell Networks Reveals Functional Role of Glutamate Receptors in Angiogenesis

Sailem

Zen

2019

Preprint

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Angiogenesis plays a key role in several diseases including cancer, ischemic vascular disease, and Alzheimer's disease. High throughput screening of endothelial tube formation provides a robust approach for identifying drugs that impact microvascular network formation and morphology. However, the analysis of resulting imaging datasets has been limited to a few phenotypic features such as the total tube length or the number of branching points. Here we developed a high content analysis framework for detailed quantification of various aspects of network morphology including network complexity, symmetry and topology. By applying our approach to a high content screen of 1,280 drugs, we found that many drugs that result in a similar phenotype share the same mechanism of action or common downstream signalling pathways. Our multiparametric analysis revealed a group of drugs, that target glutamate receptors, results in enhanced branching and network connectivity. Using an integrative meta-analysis approach, we validated the link between these receptors and angiogenesis. We further found that the expression of these genes correlates with the prognosis of Alzheimer's patients. In conclusion, our work shows that detailed image analysis of complex endothelial phenotypes can reveal new insights into biological mechanisms modulating the morphogenesis of endothelial networks and identify potential therapeutics for angiogenesisrelated diseases.

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“…The fact that deprivation of extracellular Ca 2+ leads to cell growth arrest in G1/S indicates that Ca 2+ is required for cell cycle progression. [25][26][27] One of the Ca 2+ regulation mechanisms is binding of calcium to calmodulin protein. Intracellular Ca 2+ binds with calmodulin II, in turn activates calcium-calmodulin-dependent protein kinases, and regulates pro-survival transcriptional proteins.…”

Section: Discussionmentioning

confidence: 99%

Anti-Angiogenic Activity of Flunarizine by <i>In Ovo, In Vitro</i>, and <i>In Vivo</i> Assays

Kamili¹,

Kakaraparthy²,

Vattikuti³

2019

tjps

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Hücre proliferasyonunda T-tipi kalsiyum kanallarının tutulumu ve hücre göçü içindeki sodyum kanallarının rolü anjiyogenezde kapsamlı olarak incelenmiştir. Bu çalışmada, ikili bir sodyum/kalsiyum kanal blokeri olan flunarizin; anti-anjiyojenik potansiyelini değerlendirmek için seçildi. Bu, patolojik olarak aşırı anjiyogenezin neden olduğu hastalıklarda terapötik olarak yararlı olabilir. Gereç ve Yöntemler: İyon kanalı blokörünün anti-anjiyojenik aktivitesi, civciv korioallantoik membran deneyi (in ovo), sıçan aortik halka deneyi, endotelyal hücre proliferasyon analizi, transwell migrasyon deneyi, Matrigel kord benzeri morfojenez deneyi (in vitro) ve sünger implantasyonu ile tarandı. Yöntem (in vivo). Test ilacının anti-anjiyogenik aktivitesi standart anti-anjiyojenik ilaç olan bevacizumab ile karşılaştırıldı ve buna ek olarak, test yanıtları, 500 mM'lik bir maksimum konsantrasyonda anjiyojenik faktör vasküler endotel büyüme faktörü ile karşılaştırıldı. Bulgular: Tüm gruplar kontrol grubu ile tek yönlü ANOVA kullanılarak ve post hoc testi ile karşılaştırıldı, Dunnett testi ile tüm grupların ortalamaları kontrol ortalaması ile karşılaştırıldı. Chick chorioallantoic membran testinde dallanma noktaları ve anjiyojenik skorlar değerlendirildi ve 10-5 M ve 10-4 M'de anlamlı sonuçlar gözlendi. Aort halkası analizinde, filiz alanında 5-10 µM azalma gözlendi ve sünger implantasyon yönteminde test edilen Objectives: The involvement of T-type calcium channels in cell proliferation and the role of sodium channels in cell migration have been extensively studied in angiogenesis. In the present study, flunarizine, a dual sodium/calcium channel blocker; was selected to evaluate its anti-angiogenic potential. This can be therapeutically beneficial in diseases caused by pathologically excessive angiogenesis. Materials and Methods: The anti-angiogenic activity of ion channel blocker was screened by chick chorioallantoic membrane assay (in ovo), rat aortic ring assay, endothelial cell proliferation assay, transwell migration assay, Matrigel cord-like morphogenesis assay (in vitro), and sponge implantation method (in vivo). The anti-angiogenic activity of the test drug was compared with the standard anti-angiogenic drug bevacizumab and, in addition, the test responses were compared with the angiogenic factor vascular endothelial growth factor at a maximal concentration of 500 pM. Results: All the groups were compared with the control group using one-way ANOVA, followed by a post hoc test, Dunnett's test, to compare the mean of all the groups with the control mean. In the chick chorioallantoic membrane assay, the number of branching points and angiogenic score were evaluated and significant results were observed at 10-5 M and 10-4 M. In the aortic ring assay a reduction in the area of sprouts was observed with 5-10 µM and significant reductions in the weight of sponges, number of blood vessels formed, and hemoglobin content were observed at all three tested concentrations of flunarizine in the sponge implantation method. In the studies ...

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ATP-Sensitive Potassium Channel Activation Induces Angiogenesis In Vitro and In Vivo

Cited by 32 publications

References 60 publications

Regulation and role of endogenously produced hydrogen sulfide in angiogenesis

Regulation and role of endogenously produced hydrogen sulfide in angiogenesis

Multi-Parametric Profiling of Endothelial Cell Networks Reveals Functional Role of Glutamate Receptors in Angiogenesis

Anti-Angiogenic Activity of Flunarizine by <i>In Ovo, In Vitro</i>, and <i>In Vivo</i> Assays

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