Circulation research
-
A hallmark of the vascular remodeling process underlying pulmonary hypertension (PH) is the aberrant proliferation and migration of pulmonary arterial smooth muscle cells (PASMC). Accumulating evidence suggests that mast cell mediators play a role in the pathogenesis of PH. ⋯ Our study identified a novel role of PAR-2 in vascular remodeling in the lung. Interference with this pathway may offer novel therapeutic options for the treatment of PH.
-
Circulation research · Apr 2012
The interferon stimulated gene 12 inactivates vasculoprotective functions of NR4A nuclear receptors.
Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection. ⋯ These findings identify a previously unrecognized feedback loop activated by interferons that inhibits the vasculoprotective functions of NR4A nuclear receptors, providing a potential new therapeutic target for interferon-driven pathologies.
-
Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and in cardiovascular aging. ⋯ Both cardiac and vascular aging involve neurohormonal signaling (eg, renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics, and exercise training.
-
Circulation research · Apr 2012
ReviewContribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities.
The prevalence of cardiovascular disease increases with advancing age. Although long-term exposure to cardiovascular risk factors plays a major role in the etiopathogenesis of cardiovascular disease, intrinsic cardiac aging enhances the susceptibility to developing heart pathologies in late life. The progressive decline of cardiomyocyte mitochondrial function is considered a major mechanism underlying heart senescence. ⋯ The efficiency of this process declines with advancing age, which may play a critical role in heart senescence and age-related cardiovascular disease. The present review illustrates the putative mechanisms whereby alterations in the autophagic removal of damaged mitochondria intervene in the process of cardiac aging and in the pathogenesis of specific heart diseases that are especially prevalent in late life (eg, left ventricular hypertrophy, ischemic heart disease, heart failure, and diabetic cardiomyopathy). Interventions proposed to counteract cardiac aging through improvements in macroautophagy (eg, calorie restriction and calorie restriction mimetics) are also presented.