Vascular remodeling in pulmonary hypertension.
Vascular remodeling in pulmonary hypertension.
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DOI：
10.1007/s00109-013-0998-0
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发表时间：
2013-03
影响因子：
4.7
通讯作者：
Laurie, Steven S.
中科院分区：
文献类型：
--
作者：
Shimoda, Larissa A.;Laurie, Steven S.
关键词：
肺动脉高压是一种复杂的、进行性的疾病，由多种遗传和致病原因引起。患者呈现一系列组织学和病理生理学特征，可能反映了潜在发病机制的多样性。血管壁的结构改变是所有形式肺动脉高压的原因之一。肺动脉高压患者中重塑血管系统的特征包括弹性近端肺动脉硬化增加、肌性动脉内膜和/或中层增厚、血管闭塞性病变的发展以及在正常非肌性小直径血管中出现表达平滑肌特异性标志物的细胞，这是由肺动脉平滑肌细胞的增殖和迁移以及细胞转分化引起的。几种肺动脉高压动物模型的开发提供了探索肺血管重构的机制基础的手段，尽管目前使用的实验模型都没有完全复制患者中观察到的肺动脉高压。在这里，我们提供了一个概述的组织学异常观察到的人类肺动脉高压和临床前模型，并讨论了有关几个关键的信号通路有助于重塑过程中获得的见解。特别是，我们将专注于离子稳态，内皮素-1，5-羟色胺，骨形态发生蛋白，Rho激酶和缺氧诱导因子1在肺动脉平滑肌和内皮细胞中的作用，突出这些途径之间的串扰领域和潜在的治疗靶向。
Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions and the appearance of cells expressing smooth muscle specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular trans-differentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting.
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DOI：
10.1164/ajrccm.149.2.8306040
发表时间：
1994-02-01
影响因子：
24.7
作者：
BARBERA, JA;RIVEROLA, A;RODRIGUEZROISIN, R
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DOI：
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发表时间：
2003-08-05
影响因子：
11.1
作者：
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DOI：
10.1152/ajplung.1998.275.3.l442
发表时间：
1998-09-01
影响因子：
4.9
作者：
Cutaia, MV;Parks, N;Sun, AM
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Sun, AM