Sirtuins: Possible clinical implications in cardio and cerebrovascular diseases

The mammalian sirtuins (SIRT1-7) are NAD+ dependent deacetylases involved in aging and in a wide range of cellular functions by regulating histones and several transcription factors. SIRT1, the best-characterized member of the family, acts as sensor of stress to address the cells forwards an appropriate defense. A large body of evidence has showed that SIRT1 induces both cellular and systemic protective effects in the cardiovascular system by preventing stress-induced apoptosis and senescence and ameliorating the endothelial dysfunction. Hence, SIRT1 is now indicated as potential therapeutic target for a number of cardiovascular diseases. Recently, it was suggested that the activation of SIRT1 could be also represent a neuroprotective strategy. Indeed, SIRT1 protects against ischemia/reperfusion injury both in vitro and in vivo and attenuates severe ischemic damage by preserving cerebral blood flow. Moreover, SIRT1 genetic and pharmacological manipulation could counteract the stroke outcome. In the last years it was suggested that others sirtuins, especially SIRT3 and SIRT6, could exert beneficial effects in the vascular syndromes. The present review is aimed to describe the recent experimental evidence on the effects of SIRT1 and the other sirtuins in the pathophysiology of cardio- and cerebro-vascular diseases, underlying a potential therapeutic effect of these enzymes in treatment and/or prevention of such conditions.