title: p66(Shc) protein, oxidative stress, and cardiovascular complications of diabetes: the missing link.
abstract: Diabetes affects more than 150 million people worldwide, and it is estimated that this would increase to 299 million by the year 2025. The incidence of and mortality from cardiovascular disease are two- to eightfold higher in subjects with diabetes than in those without, coronary artery disease accounting for the large majority of deaths. Among the full spectrum of biochemical effects of high glucose, generation of oxygen-derived free radicals is one of the main pathophysiological mechanisms linking hyperglycemia to atherosclerosis, nephropathy, and cardiomyopathy. The adaptor protein p66(Shc) is implicated in mitochondrial reactive oxygen species (ROS) generation and translation of oxidative signals into apoptosis. Indeed, p66(Shc-/-) mice display prolonged lifespan, reduced production of intracellular oxidants, and increased resistance to oxidative stress-induced apoptosis. Accordingly, a series of studies defined the pathophysiological role of p66(Shc) in cardiovascular disease where ROS represent a substantial triggering component. As p66(Shc) modulates the production of cellular ROS, it represents a proximal node through which high glucose exerts its deleterious effects on different cell types; indeed, several studies tested the hypothesis that deletion of the p66(Shc) gene may confer protection against diabetes-related cardiovascular complications. The present review focuses on the reported evidence linking p66(Shc) signaling pathway to high glucose-associated endothelial dysfunction, atherogenesis, nephropathy, and cardiomyopathy.
authors: Cardiology, 2nd Faculty of Medicine, Sapienza University of Rome, Sant'Andrea Hospital, Via di Grottarossa, 1035-39, 00189, Rome, Italy.
authors: Pietro
authors: P
authors: Francia
authors: Francesco
authors: F
authors: Cosentino
authors: Marzia
authors: M
authors: Schiavoni
authors: Yale
authors: Y
authors: Huang
authors: Enrico
authors: E
authors: Perna
authors: Giovani G
authors: GG
authors: Camici
authors: Thomas F
authors: TF
authors: Lüscher
authors: Massimo
authors: M
authors: Volpe
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1