Cellular and molecular pathobiology of pulmonary arterial hypertension
Cellular and molecular pathobiology of pulmonary arterial hypertension
复制标题
DOI：
10.1016/j.jacc.2004.02.029
复制
发表时间：
2004-06-16
影响因子：
24
通讯作者：
Rabinovitch, M
中科院分区：
文献类型：
--
作者：
Humbert, M;Morrell, NW;Rabinovitch, M
肺动脉高压(PAH)具有多因素的病理生物学特征。血管收缩、肺血管壁重构和血栓形成是PAH肺血管阻力增加的原因。肺血管重塑的过程涉及到血管壁的所有层面，并因肺动脉壁每个隔室内的细胞异质性而变得复杂。事实上，每种细胞类型(内皮细胞、平滑肌细胞和成纤维细胞)，以及炎症细胞和血小板，都可能在PAH中发挥重要作用。肺血管收缩被认为是肺动脉高压过程的早期组成部分。过度的血管收缩与钾通道的功能或表达异常以及内皮功能障碍有关。内皮功能障碍会导致一氧化氮和前列环素等血管扩张剂的慢性损害，以及内皮素(ET)-1等血管收缩因子的过度表达。这些异常中的许多不仅提高血管张力和促进血管重塑，而且是合理的药理靶点。最近的遗传学和病理生理学研究强调了几种介质在这种疾病中的相关性，包括前列环素、一氧化氮、ET-1、血管生成素-1、5-羟色胺、细胞因子、趋化因子以及转化生长因子-β超家族成员。在PAH中，细胞外基质的无序蛋白分解也很明显。未来的研究需要找出这些异常中的哪一种会引发PAH，以及哪些是治愈这种疾病的最佳靶点。(C)2004年，由美国心脏病学会基金会提供。
Pulmonary arterial hypertension (PAH) has a multifactorial pathobiology. Vasoconstriction, remodeling of the pulmonary vessel wall, and thrombosis contribute to increased pulmonary vascular resistance in PAH. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by cellular heterogeneity within each compartment of the pulmonary arterial wall. Indeed, each cell type (endothelial, smooth muscle, and fibroblast), as well as inflammatory cells and platelets, may play a significant role in PAH. Pulmonary vasoconstriction is believed to be an early component of the pulmonary hypertensive process. Excessive vasoconstriction has been related to abnormal function or expression of potassium channels and to endothelial dysfunction. Endothelial dysfunction leads to chronically impaired production of vasodilators such as nitric oxide and prostacyclin along with overexpression of vasoconstrictors such as endothelin (ET)-1. Many of these abnormalities not only elevate vascular tone and promote vascular remodeling but also represent logical pharmacological targets. Recent genetic and pathophysiologic studies have emphasized the relevance of several mediators in this condition, including prostacyclin, nitric oxide, ET-1, angiopoietin-1, serotonin, cytokines, chemokines, and members of the transforming-growth-factor-beta superfamily. Disordered proteolysis of the extracellular matrix is also evident in PAH. Future studies are required to find which if any of these abnormalities initiates PAH and which ones are best targeted to cure the disease. (C) 2004 by the American College of Cardiology Foundation.