State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, New Building 507, Beijing, 100005, People's Republic of China.
Curr Mol Med. 2013 Jan;13(1):155-64.
Aging is one of the greatest risk factors in vascular diseases (VDs). During aging, there are structural and functional changes in the vasculature, including dilated lumen, altered intimal-medial thickness (IMT), vascular stiffness, endothelial dysfunction, increased endothelial apoptosis, matrix metalloproteinase (MMP) dysregulation, increased expression of inflammatory molecules, aggravated oxidative stress and shortened telomere length. These changes leave the body more susceptible to primary hypertension, stroke and coronary artery disease. Molecules that suppress these age-related changes would provide an excellent medical intervention for VDs. Mammalian Sir2 (SIRT1, a NAD+-dependent deacetylase), previously shown to extend the lifespan of lower organisms, is a promising target molecule to influence some aspects of vascular aging. In this review, we summarized roles of SIRT1 in various pathophysiological processes of vascular aging and proposed that SIRT1 and its activators can become novel therapeutic targets for age-related VDs.
衰老是血管疾病(VDs)的最大风险因素之一。在衰老过程中,血管会发生结构和功能上的变化,包括管腔扩张、内膜-中膜厚度改变(IMT)、血管僵硬、内皮功能障碍、内皮细胞凋亡增加、基质金属蛋白酶(MMP)失调、炎症分子表达增加、氧化应激加重和端粒缩短。这些变化使身体更容易患上原发性高血压、中风和冠心病。抑制这些与年龄相关的变化的分子将为 VD 提供极好的医学干预。哺乳动物 Sir2(SIRT1,一种 NAD+依赖性去乙酰化酶),先前被证明可以延长低等生物的寿命,是一个有前途的靶分子,可以影响血管衰老的某些方面。在这篇综述中,我们总结了 SIRT1 在血管衰老的各种病理生理过程中的作用,并提出 SIRT1 及其激活剂可以成为与年龄相关的 VD 的新的治疗靶点。