Costa Rafael M, Neves Karla B, Tostes Rita C, Lobato Núbia S
Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil.
Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Front Physiol. 2018 Mar 21;9:253. doi: 10.3389/fphys.2018.00253. eCollection 2018.
Obesity is associated with increased risk of premature death, morbidity, and mortality from several cardiovascular diseases (CVDs), including stroke, coronary heart disease (CHD), myocardial infarction, and congestive heart failure. However, this is not a straightforward relationship. Although several studies have substantiated that obesity confers an independent and additive risk of all-cause and cardiovascular death, there is significant variability in these associations, with some lean individuals developing diseases and others remaining healthy despite severe obesity, the so-called metabolically healthy obese. Part of this variability has been attributed to the heterogeneity in both the distribution of body fat and the intrinsic properties of adipose tissue depots, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, hormonal control, thermogenic ability, and vascularization. In obesity, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. The adventitial fat layer, also known as perivascular adipose tissue (PVAT), is of major importance. Similar to the visceral adipose tissue, PVAT has a pathophysiological role in CVDs. PVAT influences vascular homeostasis by releasing numerous vasoactive factors, cytokines, and adipokines, which can readily target the underlying smooth muscle cell layers, regulating the vascular tone, distribution of blood flow, as well as angiogenesis, inflammatory processes, and redox status. In this review, we summarize the current knowledge and discuss the role of PVAT within the scope of adipose tissue as a major contributing factor to obesity-associated cardiovascular risk. Relevant clinical studies documenting the relationship between PVAT dysfunction and CVD with a focus on potential mechanisms by which PVAT contributes to obesity-related CVDs are pointed out.
肥胖与过早死亡、多种心血管疾病（CVD）的发病率和死亡率增加相关，这些疾病包括中风、冠心病（CHD）、心肌梗死和充血性心力衰竭。然而，这种关系并非简单直接。尽管多项研究证实肥胖会增加全因死亡和心血管死亡的独立及附加风险，但这些关联存在显著差异，一些瘦人会患疾病，而另一些人尽管严重肥胖却保持健康，即所谓的代谢健康型肥胖。这种差异部分归因于体脂分布的异质性以及脂肪组织库的内在特性，包括发育起源、脂肪生成和增殖能力、葡萄糖和脂质代谢、激素控制、产热能力和血管形成。在肥胖状态下，这些特定部位的差异转化为特定的脂肪分布模式，这与不同的心脏代谢风险密切相关。外膜脂肪层，也称为血管周围脂肪组织（PVAT），至关重要。与内脏脂肪组织类似，PVAT在心血管疾病中具有病理生理作用。PVAT通过释放多种血管活性因子、细胞因子和脂肪因子来影响血管稳态，这些因子可直接作用于下层平滑肌细胞层，调节血管张力、血流分布以及血管生成、炎症过程和氧化还原状态。在本综述中，我们总结了当前的知识，并讨论了PVAT在脂肪组织范围内作为肥胖相关心血管风险的主要促成因素的作用。指出了相关临床研究，这些研究记录了PVAT功能障碍与心血管疾病之间的关系，重点关注PVAT导致肥胖相关心血管疾病的潜在机制。
