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(Circulation Research. 2006;99:1.)
© 2006 American Heart Association, Inc.

Editorials

Diabetic Cardiomyopathy

A "Cardiac Stem Cell Disease" Involving p66Shc, an Attractive Novel Molecular Target for Heart Failure Therapy

Elisa Messina, Alessandro Giacomello

From the Department of Experimental Medicine and Pathology, University of Rome "La Sapienza", Rome, Italy.

Correspondence to Dr Alessandro Giacomello, University of Rome "la Sapienza", Experimental Medicine and Pathology, viale Regina Elena 324, Rome 00161, Italy. E-mail alessandro.giacomello@uniroma1.it

See related article, pages 42–52

Key Words: diabetes • cardiac stem cells • p66Shc

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Diabetes, as well as hypertension and aging, have similar effects on heart dysfunction, resulting in left ventricular hypertrophy and stiffness. These three pathological states share two common points of no return: oxidative stress and ROS formation.

Research in this area is not new. For the past 30 to 40 years, basic and pharmacological research has focused on efforts to block the production or counteract the effects of these highly reactive, unstable molecules. It is only in the last few years that, their direct toxic role in cellular structures notwithstanding, ROS has been regarded as a second messenger.¹ This represents a more subtle and insidious mechanism of action, because their byproduct and amplified effects may depend on activated cascades leading to persistent consequences (apoptosis, necrosis), even if ROS are naturally or pharmacologically contrasted.

In this regard the adaptor protein p66Shc, which along with p46Shc and p52Shc, is encoded by the ShcA gene, has been demonstrated to be a target of ROS.² p46Shc and p52Shc are ubiquitous isoforms, derived from the same mRNA through alternative start sites.³ In contrast, p66Shc expression is restricted to certain cell types and stimulatory conditions through epigenetic modifications of its distinct promoter.^4–5 Shc is tyrosine-phosphorylated in response to growth factors and Ang II.^2–6 Once phosphorylated, Shc forms a complex with Grb2, recruiting the Son-of-sevenless (SOS) exchange protein to the plasma membrane for activation of Ras. The three Shc isoforms have distinct physiological roles. In particular, whereas both p46Shc and p52Shc promote cellular proliferation and differentiation via Ras . . . [Full Text of this Article]

Related Article:

Diabetes Promotes Cardiac Stem Cell Aging and Heart Failure, Which Are Prevented by Deletion of the p66^shc Gene

Marcello Rota, Nicole LeCapitaine, Toru Hosoda, Alessandro Boni, Antonella De Angelis, Maria Elena Padin-Iruegas, Grazia Esposito, Serena Vitale, Konrad Urbanek, Claudia Casarsa, Marco Giorgio, Thomas F. Lüscher, Pier Giuseppe Pelicci, Piero Anversa, Annarosa Leri, and Jan Kajstura
Circ. Res. 2006 99: 42-52. [Abstract] [Full Text] [PDF]

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