血管周围脂肪组织在血管衰老中的作用及干预药物

The Role of Perivascular Adipose Tissue in Vascular Aging and Intervention Drugs

关键词:  血管衰老  血管周围脂肪组织  脂肪因子  促炎细胞因子

Key words:  vascular aging  perivascular adipose tissue  adipokines  pro-inflammatory cytokines

摘要:

心血管疾病是全球死亡主要原因，而血管衰老与心血管疾病的发生发展密不可分，脉管系统老化过程中伴随的血管形态学和功能变化如动脉硬化，内皮功能障碍及血管重塑是多种心血管疾病的重要驱动因素。目前的研究已经揭示了包含氧化应激、线粒体功能障碍、慢性低度炎症，基因组不稳定和蛋白质失衡等在内的多种机制对血管衰老的贡献，但近期研究结果突出了血管周围脂肪组织 (perivascular adipose tissue, PVAT) 对血管生物学的独特作用。血管周围脂肪组织作为脉管系统的重要组成部分，在发挥支撑血管作用的同时,其衍生脂肪因子如脂联素、瘦素、抵抗素和促/抗炎细胞因子等以内分泌和旁分泌方式对血管氧化应激、炎症、血管重塑以及细胞衰老发挥调节作用。由此，本文就不同病理生理条件下血管周围脂肪组织分泌组变化情况及其对血管衰老的影响进行综述，并总结了靶向PVAT并通过减轻其炎症及氧化应激、诱导褐变以及调节分泌组来缓解血管衰老的药物，以期为预防血管早衰及相关心血管疾病提供新的思路。

Abstract:

Cardiovascular disease (CVD) is the leading cause of death worldwide, and vascular aging is inextricably linked to the onset and development of CVDs. Vascular morphological and functional alternations such as arterial stiffening, endothelial dysfunction and vascular remodeling that accompany the aging process of the vasculature are important drivers of many CVDs. Numerous mechanisms, such as oxidative stress, mitochondrial dysfunction, chronic low-grade inflammation, genomic instability, and protein imbalance, have been implicated in the development of vascular aging in current studies. However, recent research has brought attention to the distinct impact of perivascular adipose tissue (PVAT) on vascular biology. As an important component of the vascular system, PVAT plays a role in supporting the vasculature, while the adipokines derived from it, including adiponectin, leptin, resistin and pro-/anti-inflammatory cytokines could regulate vascular inflammation and oxidative stress, vascular remodeling and cellular senescence via an endocrine and paracrine manner. Thus, this paper reviews the changes of PVAT secretome and their impact on vascular senescence under various pathophysiological conditions, and summarizes the drugs that target PVAT to mitigate vascular aging by attenuating PVAT inflammation and oxidative stress, inducing PVAT browning, and regulating PVAT secretome, with the aim of offering fresh insight for the prevention of premature vascular senescence and related cardiovascular diseases.