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REVIEW

HIGHLIGHTED TOPIC
Physiology of the Aging Vasculature

The role of p66^Shc deletion in age-associated arterial dysfunction and disease states

¹Cardiovascular Research, Institute of Physiology, and Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland; ²Department of Cardiology, Cardiovascular Center, University Hospital, Zurich, Switzerland; and ³Division of Cardiology, Second Faculty of Medicine, University "La Sapienza" Ospedale Sant'Andrea, Rome, Italy

Submitted 28 April 2008 ; accepted in final form 27 August 2008

ABSTRACT

Accumulation of oxidative stress with age is hypothesized to be the primary causative mediator of age-associated diseases. Among different tissues, aging vessels are known to accumulate oxidative damage and undergo functional impairment. Oxidative stress affects the availability and/or balance of key regulators of vascular homeostasis and favors the development of cardiovascular disease. Reactive oxygen species are generated by different intracellular molecular pathways principally located in the cytoplasm and in the mitochondria. The mitochondrial enzyme p66^Shc is an adaptor protein and plays an important role as a redox enzyme implicated in mitochondrial eactive oxygen species generation and translation of oxidative signals into apoptosis. Mice lacking p66^Shc–/– gene display reduced production of intracellular oxidants and a 30% prolonged life span. For this reasons, a series of studies conceived to elucidate the function of p66^Shc and its possible implication in age-associated cardiovascular diseases have been carried out. Indeed, p66^Shc–/– mice have been shown to be protected from age-dependent endothelial dysfunction as well as age-related risk factors such as diabetes and hypercholesterolemia. This review focuses on delineating the role of the p66^Shc adaptor protein and its potential implication in the pathophysiology of aging and age-related cardiovascular disease.

cardiovascular disease; reactive oxygen species

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