Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA.
MedStar Cardiovascular Research Network Washington, DC, USA.
J Biol Regul Homeost Agents. 2014 Apr-Jun;28(2):169-76.
Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients.
心血管疾病是肥胖人群发病率和死亡率的主要原因。肥胖显著增加了代谢和心血管疾病发展的风险。这种风险似乎源于脂肪组织功能的破坏，导致慢性炎症状态以及脂肪细胞衍生因子的内分泌和旁分泌作用失调。反过来，这会损害血管内稳态并导致内皮功能障碍。在所有与肥胖相关的并发症中，内皮细胞表型的改变和内皮功能障碍都很常见。内皮功能障碍的一个关键方面是一氧化氮（NO）生物利用度降低。全身性促炎状态与高血糖、胰岛素抵抗、氧化应激和肾素-血管紧张素系统激活相结合，是肥胖个体的全身性紊乱，它们独立地、协同地导致 NO 生物利用度降低。另一方面，促炎细胞因子由血管周围脂肪局部产生，并通过旁分泌机制独立作用，导致内皮功能障碍和血管平滑肌细胞功能障碍，从而促进肥胖个体的血管疾病发生。有希望的发现是，肥胖引起的血管功能障碍至少在一定程度上是可逆的，通过减肥策略和促进血管健康的药物，还没有充分证明可以大规模预防肥胖的心血管并发症。在这篇综述中，我们讨论了肥胖患者炎症和血管损伤的病理生理机制。
