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• W2289692514 abstract "<b><i>Background:</i></b> Podocytes are major components of the filtration barrier and a renal source of vascular endothelial growth factor (VEGF). Chronic renovascular disease (RVD) progressively degrades the renal function, accompanied by podocyte damage and a progressive reduction in VEGF. We showed that the endothelin (ET) pathway contributes to this pathological process and ET-A (but not ET-B) receptor antagonism protects the kidney in RVD. We hypothesize that ET-A-induced renoprotection is largely driven by the protection of podocyte integrity and function. <b><i>Methods:</i></b> To mimic the renal environment of chronic RVD, human podocytes were incubated under chronic hypoxia for 96 h and divided in untreated or treated with an ET-A or ET-B receptor antagonist. Cells were quantified after 96 h. Cell homogenates and media were obtained after 1, 24 and 96 h to quantify production of VEGF, anti-VEGF soluble receptor s-Flt1, and the expression of apoptotic mediators. A separate set of similar experiments was performed after addition of a VEGF-neutralizing antibody (VEGF-NA). <b><i>Results:</i></b> Hypoxia decreased podocyte number, which was exacerbated by ET-B but improved after ET-A antagonism. Production of VEGF was preserved by ET-A antagonism, whereas s-Flt1 increased in hypoxic cells after ET-B antagonism only, accompanied by a greater expression of pro-apoptotic mediators. On the other hand, treatment with VEGF-NA diminished ET-A-induced protection of podocytes. <b><i>Conclusion:</i></b> ET-A antagonism preserves podocyte viability and integrity under chronic hypoxia, whereas ET-B antagonism exacerbates podocyte dysfunction and death. Enhanced bioavailability of VEGF after ET-A antagonism could be a pivotal mechanism of podocyte protection that significantly contributes to ET-A receptor blockade-induced renal recovery in chronic RVD." @default.
• W2289692514 created "2016-06-24" @default.
• W2289692514 creator A5046461177 @default.
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• W2289692514 date "2016-01-01" @default.
• W2289692514 modified "2023-09-23" @default.
• W2289692514 title "Vascular Endothelial Growth Factor and Podocyte Protection in Chronic Hypoxia: Effects of Endothelin-A Receptor Antagonism" @default.
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• W2289692514 doi "https://doi.org/10.1159/000444719" @default.
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