کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1906989 1046329 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction
چکیده انگلیسی

Overproduction of reactive oxygen species in aging tissues has been implicated in the pathogenesis of aging-associated cardiovascular dysfunction. Oxidant-induced DNA-damage activates the poly(ADP-ribose) polymerase (PARP) pathway, leading to tissue injury. In this study we investigated the acute effects of the PARP inhibitor INO-1001 on aging-associated cardiac and endothelial dysfunction. Using a pressure–volume conductance catheter, left ventricular pressure–volume analysis of young and aging rats was performed before and after a single injection of INO-1001. Endothelium-dependent and -independent vasorelaxation of isolated aortic rings were investigated by using acetylcholine and sodium nitroprusside. Aging animals showed a marked reduction of myocardial contractility and endothelium-dependent relaxant responsiveness of aortic rings. Single dose INO-1001-treatment resulted in acute improvement in their cardiac and endothelial function. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) confirmed enhanced nitro-oxidative stress and PARP-activation in aging animals. Acute treatment with INO-1001 decreased PARP-activation, but did not affect nitrotyrosine-immunoreactivity. Our results demonstrate that the aging-associated chronic cardiovascular dysfunction can be improved, at least, short term, by a single treatment course with a PARP-inhibitor, supporting the role of the nitro-oxidative stress – PARP – pathway in the age-related functional decline of the cardiovascular system. Pharmacological inhibition of PARP may represent a novel therapeutic utility to improve aging-associated cardiovascular dysfunction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Gerontology - Volume 42, Issue 7, July 2007, Pages 676–685
نویسندگان
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