Journal of cardiovascular pharmacology and therapeutics
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J. Cardiovasc. Pharmacol. Ther. · Sep 2013
Randomized Controlled Trial Comparative StudyEffects of direct renin inhibition on atherosclerotic biomarkers in patients with stable coronary artery disease and type 2 diabetes mellitus.
To evaluate whether the direct renin inhibitor, aliskiren, has a more favorable effect compared to amlodipine on atherosclerotic biomarkers in patients with stable coronary artery disease and diabetes currently receiving standard secondary prevention therapy. ⋯ Treatment with either aliskiren or amlodipine did not significantly alter surrogate biomarkers of atherosclerosis in patients with both diabetes and established cardiovascular disease already receiving appropriate secondary cardiovascular prevention therapy. The study is limited in its size and duration to see an effect.
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J. Cardiovasc. Pharmacol. Ther. · Sep 2013
Protease-activated receptor 1 inhibition by SCH79797 attenuates left ventricular remodeling and profibrotic activities of cardiac fibroblasts.
Fibroblast activity promotes adverse left ventricular (LV) remodeling that underlies the development of ischemic cardiomyopathy. Transforming growth factor-β (TGF-β) is a potent stimulus for fibrosis, and the extracellular signal-regulated kinases(ERK) 1/2 pathway also contributes to the fibrotic response. The thrombin receptor, protease-activated receptor 1 (PAR1), has been shown to play an important role in the excessive fibrosis in different tissues. The aim of this study was to investigate the influence of a PAR1 inhibitor, SCH79797, on cardiac fibrosis, tissue stiffness and postinfarction remodeling, and effects of PAR1 inhibition on thrombin-induced TGF-β and (ERK) 1/2 activities in cardiac fibroblasts. ⋯ These studies suggest PAR1 inhibition initiated after ischemic injury attenuates adverse LV remodeling through late-stage antifibrotic events.