Corbi Graziamaria, Bianco Andrea, Turchiarelli Viviana, Cellurale Michele, Fatica Federica, Daniele Aurora, Mazzarella Gennaro, Ferrara Nicola
Department of Medicine and Health Sciences, University of Molise, via Giovanni Paolo II - Loc. Tappino, 86100 Campobasso, Italy.
Int J Mol Sci. 2013 Jun 17;14(6):12696-713. doi: 10.3390/ijms140612696.
The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems.
动脉粥样硬化的发展是一个多步骤过程，至少部分受血管内皮功能控制。在人类和动脉粥样硬化实验模型中的观察已将单核细胞募集确定为动脉粥样硬化发生的早期事件。慢性炎症与衰老及其相关疾病（如动脉粥样硬化和慢性阻塞性肺疾病）有关。最近发现，沉默调节蛋白（烟酰胺腺嘌呤二核苷酸依赖性脱乙酰酶）是长寿和健康的关键调节因子。它们似乎在血管生物学中具有重要作用，并调节与年龄相关的动脉粥样硬化的各个方面。许多研究表明，SIRT1在体外（如脂肪酸诱导的炎症）、体内（如动脉粥样硬化、基因敲除小鼠正常免疫功能的维持）和临床研究（如慢性阻塞性肺疾病患者）中均表现出抗炎特性。由于暴露于香烟烟雾的啮齿动物肺部和慢性阻塞性肺疾病（COPD）患者肺部的SIRT1显著减少，激活SIRT1可能是慢性阻塞性肺疾病治疗的潜在靶点。我们综述了COPD-CVD共存中涉及的炎症机制以及SIRT1在这些系统调节中的潜在作用。
