Basement Membrane Extracellular Matrix Proteins in Pulmonary Vascular and Right Ventricular Remodeling in Pulmonary Hypertension

被引:28
作者
Ambade, Anjira S. [1 ]
Hassoun, Paul M. [1 ]
Damico, Rachel L. [1 ]
机构
[1] Johns Hopkins Univ, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA
基金
美国国家卫生研究院;
关键词
pulmonary arterial hypertension; vascular remodeling; right ventricle; extracellular matrix; basement membrane; ENDOTHELIAL-CELL MIGRATION; RAT CARDIAC FIBROBLASTS; LAMININ ALPHA-2 CHAIN; SMOOTH-MUSCLE-CELLS; IV COLLAGEN; GENE-EXPRESSION; GROWTH-FACTOR; STIMULATES PROLIFERATION; MATRICELLULAR PROTEINS; ARTERIAL-HYPERTENSION;
D O I
10.1165/rcmb.2021-0091TR
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The extracellular matrix (ECM), a highly organized network of structural and nonstructural proteins, plays a pivotal role in cellular and tissue homeostasis. Changes in the ECM are critical for normal tissue repair, whereas dysregulation contributes to aberrant tissue remodeling. Pulmonary arterial hypertension is a severe disorder of the pulmonary vasculature characterized by pathologic remodeling of the pulmonary vasculature and right ventricle, increased production and deposition of structural and nonstructural proteins, and altered expression of ECM growth factors and proteases. Furthermore, ECM remodeling plays a significant role in disease progression, as several dynamic changes in its composition, quantity, and organization are documented in both humans and animal models of disease. These ECM changes impact vascular cell biology and affect proliferation of resident cells. Furthermore, ECM components determine the tissue architecture of the pulmonary and myocardial vasculature as well as the myocardium itself and provide mechanical stability crucial for tissue homeostasis. However, little is known about the basement membrane (BM), a specialized, self-assembled conglomerate of ECM proteins, during remodeling. In the vasculature, the BM is in close physical association with the vascular endothelium and smooth muscle cells. While in the myocardium, each cardiomyocyte is enclosed by a BM that serves as the interface between cardiomyocytes and the surrounding interstitial matrix. In this review, we provide a brief overview on the current state of knowledge of the BM and its ECM composition and their impact on pulmonary vascular remodeling and right ventricle dysfunction and failure in pulmonary arterial hypertension.
引用
收藏
页码:245 / 258
页数:14
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