Vascular pharmacology
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Vascular pharmacology · Jan 2012
Resveratrol reverses monocrotaline-induced pulmonary vascular and cardiac dysfunction: a potential role for atrogin-1 in smooth muscle.
Arterial remodeling contributes to elevated pulmonary artery (PA) pressures and right ventricular hypertrophy seen in pulmonary hypertension (PH). Resveratrol, a sirtuin-1 (SIRT1) pathway activator, can prevent the development of PH in a commonly used animal model, but it is unclear whether it can reverse established PH pathophysiology. Furthermore, atrophic ubiquitin ligases, such as atrogin-1 and MuRF-1, are known to be induced by SIRT1 activators but have not been characterized in hypertrophic vascular disease. ⋯ In cultured human PA smooth muscle cells (hPASMC), resveratrol significantly inhibited PDGF-stimulated proliferation and cellular hypertrophy, which was also associated with improvements in atrogin-1 levels. In addition, SIRT1 inhibition augmented hPASMC proliferation, as assessed by DNA mass, and suppressed atrogin mRNA expression. These findings demonstrate an inverse relationship between indices of PH and PA atrogin expression that is SIRT1 dependent and may reflect a novel role for SIRT1 in PASMCs opposing cellular hypertrophy and proliferation.