Newman John H, Phillips John A, Loyd James E
Division of Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650, USA.
Ann Intern Med. 2008 Feb 19;148(4):278-83. doi: 10.7326/0003-4819-148-4-200802190-00006.
Pulmonary arterial hypertension (PAH) occurs as an idiopathic disease (formerly called primary pulmonary hypertension) and as a consequence of other illnesses. These illnesses include connective tissue diseases, portal hypertension, diet and stimulant drug use, HIV infection, and congenital heart disease. Inherited susceptibility to PAH occurs in families and is almost always due to mutations in genes of the TGF-beta family of receptors. The most common mutation leading to PAH is in bone morphogenetic protein receptor type 2 (BMPR2), originally discovered to be involved in bone healing. Mutations in BMPR2 have also been found in patients with idiopathic PAH, although the true prevalence of this susceptibility has not been determined. About 20% of individuals with a BMPR2 mutation develop symptomatic pulmonary hypertension. Evidence is growing that imbalanced activation of other TGF-beta receptors coupled with reduced activity of mutated BMPR2 increases the likelihood of development of PAH. Many signaling systems have been found to participate in PAH, including K channels, serotonin, angiopoietin, and cyclooxygenases. An interaction of these signaling systems with BMPR2 is a focus of research in PAH. Approaches to altering the imbalance of activation of BMPR2 and other TGF-beta receptors may yield future therapies for PAH.
肺动脉高压（PAH）可作为一种特发性疾病（以前称为原发性肺动脉高压）出现，也可作为其他疾病的结果出现。这些疾病包括结缔组织病、门静脉高压、饮食及刺激性药物使用、HIV感染和先天性心脏病。PAH的遗传易感性在家族中存在，几乎总是由于转化生长因子-β（TGF-β）受体家族基因的突变所致。导致PAH的最常见突变发生在2型骨形态发生蛋白受体（BMPR2）中，该受体最初被发现参与骨愈合。在特发性PAH患者中也发现了BMPR2的突变，尽管这种易感性的真实患病率尚未确定。约20%携带BMPR2突变的个体发生有症状的肺动脉高压。越来越多的证据表明，其他TGF-β受体的激活失衡与突变的BMPR2活性降低增加了PAH发生的可能性。已发现许多信号系统参与PAH，包括钾通道、5-羟色胺、血管生成素和环氧化酶。这些信号系统与BMPR2的相互作用是PAH研究的一个重点。改变BMPR2和其他TGF-β受体激活失衡的方法可能会为PAH带来未来的治疗方法。
