Severe pulmonary hypertension: The role of metabolic and endocrine disorders.
Severe pulmonary hypertension: The role of metabolic and endocrine disorders.
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DOI：
10.4103/2045-8932.97592
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发表时间：
2012-04
影响因子：
2.6
通讯作者：
Voelkel NF
中科院分区：
文献类型：
--
作者：
Bogaard HJ;Al Husseini A;Farkas L;Farkas D;Gomez-Arroyo J;Abbate A;Voelkel NF
肺动脉高压（PAH）是一种多因素疾病，潜在的肺血管疾病是由遗传、表观遗传和免疫相关因素的共同作用形成的。性别、肥胖和代谢综合征是否以及如何改变 PAH 和相关的右心衰竭正在接受深入研究。雌激素可以增强肺血管增殖过程，但也可以在压力下保护右心室。肥胖可能通过与炎症细胞和介质的相互作用或通过内分泌信号的改变影响肺循环。肥胖是肺静脉压升高且左心室射血分数保留的患者发生肺动脉高压的主要危险因素。鉴于 PAH 和自身免疫性疾病之间的重叠，PAH 患者的甲状腺功能减退症通常被认为是自身免疫性甲状腺炎的结果。在甲状腺机能亢进症的临床情况下，由于高动力循环可能会导致严重的肺动脉高压，但当甲状腺机能亢进症与肺动脉高压相关时，情况会更加复杂。我们最近在严重 PAH 的相关动物模型中表明，甲状腺激素通过其内皮细胞增殖作用，可以允许并驱动血管增殖。通过整合素 αvβ3 和 FGF 受体发出的信号可能参与了该 PAH 模型中肺血管病变的形成。甲状腺激素在甲状腺功能正常的 PAH 患者中是否发挥重要的病理生物学作用尚不清楚，因为我们也不知道严重 PAH 患者中常见的甲状腺功能减退症是否具有心脏保护作用。这篇简短的综述重点介绍了有关代谢和内分泌紊乱在 PAH 中的作用的一些最新见解。
Pulmonary arterial hypertension (PAH) is a multi-factorial condition and the underlying pulmonary vascular disease is shaped by the combined action of genetic, epigenetic and immune-related factors. Whether and how gender, obesity and the metabolic syndrome modify PAH and associated right heart failure is under intense investigation. Estrogens may enhance the process of pulmonary angioproliferation, but may also protect the right ventricle under pressure. Obesity may affect the pulmonary circulation via interactions with inflammatory cells and mediators, or via alterations in endocrine signaling. Obesity is a major risk factor for pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved LV ejection fraction. Given the overlap between PAH and autoimmune diseases, hypothyroidism in patients with PAH is commonly considered a consequence of an autoimmune thyroiditis. In the clinical setting of hyperthyroidism, severe pulmonary hypertension may develop due to a hyperdynamic circulation, but a more complex situation presents itself when hyperthyroidism is associated with PAH. We recently showed in a relevant animal model of severe PAH that thyroid hormone, via its endothelial cell-proliferative action, can be permissive and drive angioproliferation. Signaling via the integrin αvβ3 and FGF receptors may participate in the formation of the lung vascular lesions in this model of PAH. Whether thyroid hormones in euthyroid PAH patients play a pathobiologically important role is unknown- as we also do not know whether the commonly diagnosed hypothyroidism in patients with severe PAH is cardioprotective. This brief review highlights some recent insights into the role of metabolic and endocrine disorders in PAH.