کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1911652 1046827 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Platelet-associated NAD(P)H oxidase contributes to the thrombogenic phenotype induced by hypercholesterolemia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Platelet-associated NAD(P)H oxidase contributes to the thrombogenic phenotype induced by hypercholesterolemia
چکیده انگلیسی

Elevated cholesterol levels promote proinflammatory and prothrombogenic responses in venules and impaired endothelium-dependent arteriolar dilation. Although NAD(P)H oxidase-derived superoxide has been implicated in the altered vascular responses to hypercholesterolemia, it remains unclear whether this oxidative pathway mediates the associated arteriolar dysfunction and platelet adhesion in venules. Platelet and leukocyte adhesion in cremasteric postcapillary venules and arteriolar dilation responses to acetylcholine were monitored in wild-type (WT), Cu,Zn-superoxide dismutase transgenic (SOD-TgN), and NAD(P)H oxidase-knockout (gp91phox−/−) mice placed on a normal (ND) or high-cholesterol (HC) diet for 2 weeks. HC elicited increased platelet and leukocyte adhesion in WT mice versus ND. Cytosolic subunits of NAD(P)H oxidase (p47phox and p67phox) were expressed in platelets. This was not altered by hypercholesterolemia; however, platelets and leukocytes from HC mice exhibited elevated generation of reactive oxygen species compared to ND mice. Hypercholesterolemia-induced leukocyte recruitment was attenuated in SOD-TgN–HC and gp91phox−/−–HC mice. Recruitment of platelets derived from WT–HC mice in venules of SOD-TgN–HC or gp91phox−/−–HC recipients was comparable to ND levels. Adhesion of SOD-TgN–HC platelets paralleled the leukocyte response and was attenuated in SOD-TgN–HC recipients, but not in WT–HC recipients. However, gp91phox−/−–HC platelets exhibited low levels of adhesion comparable to those of WT–ND in both hypercholesterolemic gp91phox−/− and WT recipients. Arteriolar dysfunction was evident in WT–HC mice, compared to WT–ND. Overexpression of SOD or, to a lesser extent, gp91phox deficiency restored arteriolar vasorelaxation responses toward WT–ND levels. These findings reveal a novel role for platelet-associated NAD(P)H oxidase in producing the thrombogenic phenotype in hypercholesterolemia and demonstrate that NAD(P)H oxidase-derived superoxide mediates the HC-induced arteriolar dysfunction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 43, Issue 1, 1 July 2007, Pages 22–30
نویسندگان
, , , , ,