Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland, UK.
Department of Internal and Agricultural Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland.
Br J Pharmacol. 2017 Oct;174(20):3496-3513. doi: 10.1111/bph.13705. Epub 2017 Feb 9.
Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies, perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vaso-protective adipocyte-derived relaxing factors and increased production of paracrine factors such as resistin, leptin, cytokines (IL-6 and TNF-α) and chemokines [RANTES (CCL5) and MCP-1 (CCL2)]. These adipocyte-derived factors initiate and orchestrate inflammatory cell infiltration including primarily T cells, macrophages, dendritic cells, B cells and NK cells. Protective factors such as adiponectin can reduce NADPH oxidase superoxide production and increase NO bioavailability in the vessel wall, while inflammation (e.g. IFN-γ or IL-17) induces vascular oxidases and eNOS dysfunction in the endothelium, vascular smooth muscle cells and adventitial fibroblasts. All of these events link the dysfunctional perivascular fat to vascular dysfunction. These mechanisms are important in the context of a number of cardiovascular disorders including atherosclerosis, hypertension, diabetes and obesity. Inflammatory changes in PVAT's molecular and cellular responses are uniquely different from classical visceral or subcutaneous adipose tissue or from adventitia, emphasizing the unique structural and functional features of this adipose tissue compartment. Therefore, it is essential to develop techniques for monitoring the characteristics of PVAT and assessing its inflammation. This will lead to a better understanding of the early stages of vascular pathologies and the development of new therapeutic strategies focusing on perivascular adipose tissue.
This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.
血管周围脂肪组织（PVAT）在心血管疾病的发病机制中起着关键作用。在血管病变中，血管周围脂肪组织体积增加并功能失调，细胞组成和分子特征发生改变。PVAT 功能障碍的特征是其炎症特征、氧化应激、血管保护脂肪细胞衍生的松弛因子产生减少和旁分泌因子如抵抗素、瘦素、细胞因子（IL-6 和 TNF-α）和趋化因子[RANTES（CCL5）和 MCP-1（CCL2）]的产生增加。这些脂肪细胞衍生的因子启动并协调炎症细胞浸润，包括主要的 T 细胞、巨噬细胞、树突状细胞、B 细胞和 NK 细胞。保护性因子，如脂联素，可减少 NADPH 氧化酶超氧化物的产生，并增加血管壁中 NO 的生物利用度，而炎症（如 IFN-γ 或 IL-17）可诱导血管氧化酶和内皮细胞、血管平滑肌细胞和外膜成纤维细胞中 eNOS 功能障碍。所有这些事件都将功能失调的血管周围脂肪与血管功能障碍联系起来。这些机制在多种心血管疾病中很重要，包括动脉粥样硬化、高血压、糖尿病和肥胖症。PVAT 的分子和细胞反应中的炎症变化与经典的内脏或皮下脂肪组织或外膜明显不同，强调了这种脂肪组织隔室的独特结构和功能特征。因此，开发监测 PVAT 特征和评估其炎症的技术至关重要。这将有助于更好地理解血管病变的早期阶段，并开发专注于血管周围脂肪组织的新治疗策略。
本文是关于调节血管周围脂肪组织的分子机制的专题部分的一部分 - 潜在的药理学靶点？要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.
