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Pleiotropic Effect of Statins as Antioxidants on Cardiac Hypertrophy

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Abstract:

A number of clinical studies suggest that 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins reduce the incidence of myocardial infarction and other cardio-cerebrovascular events. Recently, the pleiotropic effects of statins have been reported in cardiovascular cells and provided a new insight into the molecular mechanism of cardiovascular and other diseases. The favorable effects of statins could be expanded to antioxidant effects. Statins can block the isoprenylation and activation of members of the Rho family, such as RhoA and Rac1. Rac1 also regulates NADPH oxidase, which is a major source of reactive oxygen species (ROS) in cardiovascular cells. Thus, statins may attenuate oxidative stress through inhibition of Rac1. Interestingly, fluvastatin showed additional hydroxyl radical scavenging activity as potent as that of well known antioxidants, dimethylthiourea and alpha-tocopherol. This antioxidant effect may be derived from the unique chemical structure of fluvastatin.

Cardiac hypertrophy is an initial physiological adaptive response of the heart to pressure overload. However, if pressure overload persists, frequently, the heart decompensates and develops “pathophysiological” hypertrophy. Growing evidence suggests that ROS may be involved in the process of cardiac hypertrophy, and recent research has shown that statins can attenuate cardiac hypertrophy through inhibition of Rac1. The new evidence of therapeutic implications of statin therapy as antioxidant therapy will likely yield important new insights.



Keywords: HMG-CoA reductase inhibitor; Rho; eNOS

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/187152208784587863

Publication date: June 1, 2008

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  • Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in the medicinal chemistry and rational drug design for the discovery of new Immunology, Endocrine & Metabolic Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Immunology, Endocrine & Metabolic medicinal chemistry.

    Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in Immunology, Endocrine & Metabolic drug discovery.
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