TY - JOUR
T1 - Final common molecular pathways of aging and cardiovascular disease
T2 - Role of the p66Shc protein
AU - Cosentino, Francesco
AU - Francia, Pietro
AU - Camici, Giovanni G.
AU - Pelicci, Pier Giuseppe
AU - Lüscher, Thomas F.
PY - 2008/4
Y1 - 2008/4
N2 - 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 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 p66 and its possible implication in cardiovascular diseases. Indeed, p66 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 p66 adaptor protein as well as on the mechanisms linking p66-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 expression and activity may be a novel and effective target for the treatment of atherosclerotic vascular disease as well as myocardial adaptation to hypertrophic, inflammatory and neuro-hormonal stimuli in the overloaded heart.
AB - 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 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 p66 and its possible implication in cardiovascular diseases. Indeed, p66 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 p66 adaptor protein as well as on the mechanisms linking p66-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 expression and activity may be a novel and effective target for the treatment of atherosclerotic vascular disease as well as myocardial adaptation to hypertrophic, inflammatory and neuro-hormonal stimuli in the overloaded heart.
KW - Aging
KW - Atherosclerosis
KW - Diabetes
KW - Energy metabolism
KW - p66
UR - http://www.scopus.com/inward/record.url?scp=42249097446&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42249097446&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.107.156059
DO - 10.1161/ATVBAHA.107.156059
M3 - Article
C2 - 18162611
AN - SCOPUS:42249097446
VL - 28
SP - 622
EP - 628
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 4
ER -