TY - JOUR
T1 - Basement membrane extracellular matrix proteins in pulmonary vascular and right ventricular remodeling in pulmonary hypertension
AU - Ambade, Anjira S.
AU - Hassoun, Paul M.
AU - Damico, Rachel L.
N1 - Funding Information:
Supported by National Institutes of Health (NIH) HL132153/R01 (P.M.H. and R.L.D.), HL114910/R01 (P.M.H. and R.L.D.).
Publisher Copyright:
Copyright © 2021 by the American Thoracic Society.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - Basement membrane
KW - Extracellular matrix
KW - Pulmonary arterial hypertension
KW - Right ventricle
KW - Vascular remodeling
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U2 - 10.1165/rcmb.2021-0091TR
DO - 10.1165/rcmb.2021-0091TR
M3 - Review article
C2 - 34129804
AN - SCOPUS:85112160179
VL - 65
SP - 245
EP - 258
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 3
ER -