Autophagy and cardiovascular aging

The biological aging process is commonly associated with increased risk of cardiovascular diseases. Several theories have been put forward for aging-associated deterioration in ventricular function, including attenuation of growth hormone (insulin-like growth factors and insulin) signaling, loss of DNA replication and repair, histone acetylation and accumulation of reactive oxygen species. Recent evidence has depicted a rather unique role of autophagy as another important pathway in the regulation of longevity and senescence. Autophagy is a predominant cytoprotective (rather than self-destructive) process. It carries a prominent role in determination of lifespan. Reduced autophagy has been associated with aging, leading to accumulation of dysfunctional or damaged proteins and organelles. To the contrary, measures such as caloric restriction and exercise may promote autophagy to delay aging and associated comorbidities. Stimulation of autophagy using rapamycin may represent a novel strategy to prolong lifespan and combat aging-associated diseases. Rapamycin regulates autophagy through inhibition of the nutrient-sensing molecule mammalian target of rapamycin (mTOR). Inhibition of mTOR through rapamycin and caloric restriction promotes longevity. The purpose of this review is to recapitulate some of the recent advances in an effort to better understand the interplay between rapamycin-induced autophagy and decelerating cardiovascular aging.     

Selenium and cardiovascular disease

For humans, ecological and epidemiological results are reported that show a relationship between the serum selenium concentration and cardiovascular disease in populations where low serum selenium concentrations are found, e.g., in Eastern Finland. From clinical studies done in Germany (FRG and GDR), Finland, and Sweden, subnormal serum selenium and partially whole blood selenium concentrations are reported in patients with acute myocardial infarction. For patients with coronary arteriosclerosis, subnormal serum selenium concentrations are reported from the USA and Germany and subnormal whole blood selenium concentrations from Germany. Subnormal serum and subnormal whole blood selenium concentrations of patients with cardiomyopathy are reported from non Keshan disease affected areas in Germany, France, and China. In selenium deficiency, an accumulation of lipid peroxides in the heart may occur, especially under ischemic conditions and if ischemic tissue is reperfused. Lipidperoxides in the heart may damage the cell membrane and may lead to an impaired calcium transport with an uncontrolled calcium accumulation in the cell. This may result in an activation of phospholipids, and, in consequence, to an enhanced formation of arachidonic acid. An increased concentration of lipid peroxides owing to selenium deficiency may shift the prostaglandin synthesis from prostacyclin to thromboxan, causing enhanced blood pressure and platelet aggregability. From animal experiments, it is known that selenium protects against cardiotoxic elements, cardiotoxic xenobiotics, and viral infections that affect the heart. Selenium deficiency may also be a secondary factor in the causation of hypertension and myocardial ischemia.     

Urotensin-II and cardiovascular remodeling

Urotensin-II (U-II), a cyclic undecapeptide, and its receptor, UT, have been linked to vascular and cardiac remodeling. In patients with coronary artery disease (CAD), it has been shown that U-II plasma levels are significantly greater than in normal patients and the severity of the disease is increased proportionally to the U-II plasma levels. We showed that U-II protein and mRNA levels were significantly elevated in the arteries of patients with coronary atherosclerosis in comparison to healthy arteries. We observed U-II expression in endothelial cells, foam cells, and myointimal and medial vSMCs of atherosclerotic human coronary arteries. Recent studies have demonstrated that U-II acts in synergy with mildly oxidized LDL inducing vascular smooth muscle cell (vSMC) proliferation. Additionally, U-II has been shown to induce cardiac fibrosis and cardiomyocyte hypertrophy leading to cardiac remodeling. When using a selective U-II antagonist, SB-611812, we demonstrated a decrease in cardiac dysfunction including a reduction in cardiomyocyte hypertrophy and cardiac fibrosis. These findings suggest that U-II is undoubtedly a potential therapeutic target in treating cardiovascular remodeling.     

MicroRNAs and cardiovascular diseases

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have gained status as important regulators of gene expression. Recent studies have demonstrated that miRNAs are aberrantly expressed in the cardiovascular system under some pathological conditions. Gain- and loss-of-function studies using in vitro and in vivo models have revealed distinct roles for specific miRNAs in cardiovascular development and physiological function. The implications of miRNAs in cardiovascular disease have recently been recognized, representing the most rapidly evolving research field. In the present minireview, the current relevant findings on the role of miRNAs in cardiac diseases are updated and the target genes of these miRNAs are summarized.     

Alcohol and cardiovascular health

The substantial medical risks of heavy alcohol drinking as wellas the existence of a safe drinking limit have been evidentfor centuries. Modern epidemiologic studies also show lowerrisk of both morbidity and mortality among lighter drinkers.Defining "heavy" as