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• W2158034314 abstract "Background and Purpose Hydrogen sulfide ( H 2 S ), an endogenous volatile mediator with pleiotropic functions, promotes vasorelaxation, exerts anti‐inflammatory actions and regulates angiogenesis. Previously, the SH ‐containing angiotensin‐converting enzyme inhibitor ( ACEI ), zofenopril, was identified as being effective in preserving endothelial function and inducing angiogenesis among ACEIs . Based on the H 2 S donor property of its active metabolite zofenoprilat, the objective of this study was to evaluate whether zofenoprilat‐induced angiogenesis was due to increased H 2 S availability. Experimental Approach HUVEC s were used for in vitro studies of angiogenesis, whereas the Matrigel plug assay was used for in vivo assessments. Key Results Zofenoprilat‐treated HUVEC s showed an increase in all functional features of the angiogenic process in vitro . As zofenoprilat induced the expression of CSE (cystathionine‐γ‐lyase) and the continuous production of H 2 S , CSE inhibition or silencing blocked the ability of zofenoprilat to induce angiogenesis, both in vitro and in vivo . The molecular mechanisms underlying H 2 S /zofenoprilat‐induced angiogenesis were dependent on A kt, eNOS and ERK 1/2 cascades. ATP ‐sensitive potassium ( K ATP ) channels, the molecular target that mediates part of the vascular functions of H 2 S , were shown to be involved in the upstream activation of A kt and ERK 1/2. Moreover, the up‐regulation of fibroblast growth factor‐2 was dependent on CSE ‐derived H 2 S response to H 2 S and K ATP activation. Conclusions and Implications Zofenoprilat induced a constant production of H 2 S that stimulated the angiogenic process through a K ATP channel/ A kt/ eNOS / ERK 1/2 pathway. Thus, zofenopril can be considered as a pro‐angiogenic drug acting through H 2 S release and production, useful in cardiovascular pathologies where vascular functions need to be re‐established and functional angiogenesis induced." @default.
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• W2158034314 date "2015-03-27" @default.
• W2158034314 modified "2023-10-18" @default.
• W2158034314 title "Characterization of zofenoprilat as an inducer of functional angiogenesis through increased H₂S availability" @default.
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• W2158034314 doi "https://doi.org/10.1111/bph.13101" @default.
• W2158034314 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4459016" @default.
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