کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2962569 1178437 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular Signaling Mediated by Angiotensin II Type 1A Receptor Blockade Leading to Attenuation of Renal Dysfunction-Associated Heart Failure
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Molecular Signaling Mediated by Angiotensin II Type 1A Receptor Blockade Leading to Attenuation of Renal Dysfunction-Associated Heart Failure
چکیده انگلیسی

BackgroundIn patients with end-stage renal disease, angiotensin II type 1A receptor (AT1) blockade attenuates the associated cardiac dysfunction. We investigated the molecular signaling mediating that effect.Methods and ResultsWe used 5/6 nephrectomy to induce significant renal dysfunction in AT1 knockout (AT1KO) and wild-type mice (WT). Twelve weeks after nephrectomy, WT showed significant left ventricular dilation and dysfunction that were accompanied by cardiomyocyte hypertrophy, fibrosis, and reduced capillary density. All of these effects were significantly mitigated in AT1KO. Nephrectomy led to upregulation of myocardial expression of AT1, transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and phosphorylated Akt (p-Akt), and also led to increased oxidative damage in cardiomyocytes. In AT1KO, TGF-β1, TIMP-1, oxidative damage levels were lower, whereas MMPs and p-Akt levels were higher. Treating nephrectomized WT mice with valsartan (an AT1 blocker), but not hydralazine, improved cardiac function and altered molecular signaling in a manner similar to that seen in AT1KO mice. Notably, AT1 expression was downregulated in valsartan-treated but not hydralazine-treated hearts.ConclusionsThese findings provide novel insight into the mechanism underlying the beneficial effects of AT1 blockade on cardiac function in a model of renal dysfunction–associated heart failure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Cardiac Failure - Volume 13, Issue 2, March 2007, Pages 155–162
نویسندگان
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