Final Common Molecular Pathways of Aging and Cardiovascular Disease

Abstract

Abstract-Oxidative stress affects the availability of key-regulators of vascular homeostasis and controls a number of signaling pathways relevant to myocardial and vascular disease. Reactive oxygen species are generated by different intracellular molecular pathways principally located in mitochondria. The notion that mice carrying a targeted mutation of the p66 Shc gene display prolonged lifespan, reduced production of intracellular oxidants, and increased resistance to oxidative stress-induced apoptosis prompted a series of studies aimed at defining the biochemical function of p66Shc and its possible implication in cardiovascular diseases. Indeed, p66ShcϪ/Ϫ mice are protected against vascular, cardiac, and renal impairment attributable to hypercholesterolemia, aging, diabetes, and ischemia/reperfusion. The present review focuses on the biochemical and physiological function of the p66Shc adaptor protein as well as on the mechanisms linking p66Shc -associated generation of free radicals to the pathophysiology of aging and cardiovascular disease. On the whole, the evidence so far reported and here discussed supports the concept that pharmacological modulation of p66

From Sirtuin Biology to Human Diseases: An Update

“…In line with a protective role for SIRT1 in cardiovascular disease, it also protects mice from hyperglycemia-induced endothelial dysfunction by inhibiting the expression of p66Shc (77). Mice deficient in p66Shc have increased resistance to oxidative stress and improved endothelial function and are protected against vascular and cardiac diseases (78). In contrast with these observations, transgenic mice overexpressing SIRT1 develop larger atherosclerotic lesions compared with control animals (24).…”

Mitochondrial disruption occurs downstream from β-adrenergic overactivation by isoproterenol in differentiated, but not undifferentiated H9c2 cardiomyoblasts: Differential activation of stress and survival pathways

“…Phosphorylation of p66Shc on serine 36 by protein kinase C beta increases during cellular stress and results in amplifying mitochondrial oxidative stress and apoptotic signaling (Cosentino et al, 2008). ISO increases the ratio between Ser36-phosphorylated p66Shc and the total p66Shc content in the two groups of differentiated cells, as opposed to undifferentiated myoblasts where a small, non-significant increase was observed (Fig.…”

Wytyczne ESC dotyczące cukrzycy, stanu przedcukrzycowego i chorób układu sercowo- -naczyniowego opracowane we współpracy z EASD

“…6) [75][76][77]. Z kolei mitochondrialne ROS aktywują kaskadę sygnałową uczestniczącą w patogenezie powikłań sercowo-naczyniowych, w skład której wchodzą szlak poliolowy, zaawansowane produkty glikacji (AGE) i ich receptory (RAGE), PKC i szlak heksozaminy (HSP) (ryc.…”