Obesity and pulmonary arterial hypertension: Is adiponectin the molecular link between these conditions?
Obesity and pulmonary arterial hypertension: Is adiponectin the molecular link between these conditions?
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DOI：
10.4103/2045-8932.93542
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发表时间：
2011-10
影响因子：
2.6
通讯作者：
Medoff BD
中科院分区：
文献类型：
--
作者：
Summer R;Walsh K;Medoff BD
肺动脉高压（PAH）是一种病因不明的疾病，其病理特征包括血管阻力增加、血管周围炎症细胞浸润以及肺小动脉重塑。尽管肺动脉高压的危险因素尚不明确，但近期研究表明，肥胖可能是这种疾病的一个重要危险因素。导致这种关联的机制在很大程度上尚不清楚，但脂肪组织分泌的生物活性介质已被认为参与了这一过程。脂肪组织释放的最重要的介质之一是脂肪因子脂联素。脂联素在健康瘦人的循环中含量很高，并具有明确的代谢和抗炎作用。脂联素水平随着体重增加而降低，其水平低下与小鼠肺动脉高压的发生直接相关。此外，脂联素的过表达已被证明可保护小鼠免受炎症和缺氧引发的肺动脉高压。基于这些研究的结果，有人提出脂联素的作用部分是通过其抗炎和抗增殖特性介导的。在这篇综述中，我们讨论了新出现的证据，这些证据表明脂联素在肺血管内稳态中起作用，并讨论了这种源自脂肪细胞的激素缺乏如何解释肥胖与肺动脉高压之间近期发现的关联。
Pulmonary arterial hypertension (PAH) is a condition of unknown etiology whose pathological features include increased vascular resistance, perivascular inflammatory cell infiltration and pulmonary arteriolar remodeling. Although risk factors for PAH are poorly defined, recent studies indicate that obesity may be an important risk factor for this condition. The mechanisms leading to this association are largely unknown, but bioactive mediators secreted from adipose tissue have been implicated in this process. One of the most important mediators released from adipose tissue is the adipokine adiponectin. Adiponectin is highly abundant in the circulation of lean healthy individuals, and possesses well-described metabolic and antiinflammatory actions. Levels of adiponectin decrease with increasing body mass, and low levels are directly linked to the development of PAH in mice. Moreover, overexpression of adiponectin has been shown to protect mice from developing PAH in response to inflammation and hypoxia. Based on the findings from these studies, it is suggested that the effects of adiponectin are mediated, in part, through its antiinflammatory and antiproliferative properties. In this review, we discuss the emerging evidence demonstrating a role for adiponectin in lung vascular homeostasis and discuss how deficiency in this adipocyte-derived hormone might explain the recent association between obesity and PAH.