Artículos de revistas
Activated Protein C Protects Against Diabetic Nephropathy By Inhibiting Endothelial And Podocyte Apoptosis
Registro en:
Nature Medicine. , v. 13, n. 11, p. 1349 - 1358, 2007.
10788956
10.1038/nm1667
2-s2.0-35948934636
Autor
Isermann B.
Vinnikov I.A.
Madhusudhan T.
Herzog S.
Kashif M.
Blautzik J.
Corat M.A.F.
Zeier M.
Blessing E.
Oh J.
Gerlitz B.
Berg D.T.
Grinnell B.W.
Chavakis T.
Esmon C.T.
Weiler H.
Bierhaus A.
Nawroth P.P.
Institución
Resumen
Data providing direct evidence for a causative link between endothelial dysfunction, microvascular disease and diabetic end-organ damage are scarce. Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally linked to nephropathy. Thrombomodulin-dependent APC formation mediates cytoprotection in diabetic nephropathy by inhibiting glomerular apoptosis. APC prevents glucose-induced apoptosis in endothelial cells and podocytes, the cellular components of the glomerular filtration barrier. APC modulates the mitochondrial apoptosis pathway via the protease-activated receptor PAR-1 and the endothelial protein C receptor EPCR in glucose-stressed cells. These experiments establish a new pathway, in which hyperglycemia impairs endothelial thrombomodulin- dependent APC formation. 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