Conti Valeria, Forte Maurizio, Corbi Graziamaria, Russomanno Giusy, Formisano Luigi, Landolfi Alessandro, Izzo Viviana, Filippelli Amelia, Vecchione Carmine, Carrizzo Albino
Vascular Pathophysiology Unit, IRCCS Neuromed, Pozzilli (IS), Italy.
Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
Curr Drug Targets. 2017;18(4):473-484. doi: 10.2174/1389450116666151019095903.
Mammalian sirtuins (SIRT1-7) are NAD+-dependent deacetylases, which play an important role in aging and in a wide range of cellular functions. SIRT1, the best-characterized member of the family, acts as a sensor of the redox state and triggers in the cell the appropriate defense response. 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 mitigating endothelial dysfunction. Hence, SIRT1 is now foreseen as a potential therapeutic target for a growing number of cardiovascular diseases. Recently, it has been suggested that SIRT1 activation could also be considered as a neuroprotective strategy. Indeed, SIRT1 protects against ischemia/reperfusion injury both in vitro and in vivo and avoids severe ischemic damage by preserving cerebral blood flow. In the last years it was suggested that others sirtuins, in particular SIRT3 and SIRT6, could exert beneficial effects in vascular syndromes. The aim of this review was to describe and discuss recent experimental evidence on the effects of SIRT1 and other sirtuins on the pathophysiology of cardio- and cerebrovascular diseases, underlying a potential therapeutic effect of these enzymes in the treatment and/or prevention of such conditions.
哺乳动物的沉默调节蛋白（SIRT1 - 7）是依赖烟酰胺腺嘌呤二核苷酸（NAD+）的去乙酰化酶，在衰老及广泛的细胞功能中发挥重要作用。该家族中研究最充分的成员SIRT1，作为氧化还原状态的传感器，在细胞内触发适当的防御反应。大量证据表明，SIRT1通过防止应激诱导的细胞凋亡和衰老以及减轻内皮功能障碍，在心血管系统中诱导细胞和全身的保护作用。因此，SIRT1现在被视为越来越多心血管疾病的潜在治疗靶点。最近，有人提出SIRT1激活也可被视为一种神经保护策略。事实上，SIRT1在体外和体内均能保护免受缺血/再灌注损伤，并通过维持脑血流量避免严重的缺血性损伤。在过去几年中，有人提出其他沉默调节蛋白，特别是SIRT3和SIRT6，可能在血管综合征中发挥有益作用。本综述的目的是描述和讨论关于SIRT1和其他沉默调节蛋白对心脑血管疾病病理生理学影响的最新实验证据，强调这些酶在治疗和/或预防此类疾病中的潜在治疗作用。
