Sirtuins, oxidative stress and angiotensin-II mediated cardiac hypertrophy: evidence from animal studies

Paul J. Lijnen, John S. Prihadi

Abstract
Angiotensin II-induced cardiac hypertrophy is associated with oxidative stress-dependent mitochondrial dysfunction. Sirtuins have recently emerged as important proteins contributing to stress resistance, cell growth, apoptosis, metabolism and aging. The involvement of sirtuins in the angiotensin II-stimulated production of reactive oxygen species and in the development of cardiac hypertrophy in animal studies will be discussed in this review article. Sirtuins play diverse roles in the cardiovascular system. This functional diversity is related to the existence of seven mammalian sirtuins and to the various molecular targets for its deacetylation and ADP ribosyltransfer reactions. In the heart SIRT-3 blocks the development of cardiac hypertrophy and protect cardiomyocytes from oxidative stress-mediated cell death. The antioxidant effect of SIRT-3 may play an important role in ameliorative hypertrophic agonist-induced cardiac hypertrophy. SIRT-3 is an endogenous negative regulator of cardiac hypertrophy by suppressing the cellular production of ROS. Undoubtedly, more research is needed to unravel the exact role of sirtuins in cardiac cell biology before they can be used as therapeutic targets valuable for translational medicine and heart failure. Whether the direct pharmacological modulation of sirtuins may confer greater benefit in cardiac diseases than the other antioxidant approaches, which shows disappointing results, is an intriguing concept.

Key words: Angiotensin II; Cardiac hypertrophy; Poly(ADP-ribose)polymerase-1; Sirtuins