Cellular and Molecular Basis of Pulmonary Arterial Hypertension
By N. Morrell, S. Adnot, S. Archer, J. Dupuis, Peter Lloyd Jones, M. MacLean, I. Mcmurtry, K. Stenmark, P. Thistlethwaite, N. Weissmann and 2 more. Journal of the American College of Cardiology, 2009
830 citations recorded by the source corpus.
Pulmonary arterial hypertension (PAH) is caused by functional and structural changes in the pulmonary vasculature, leading to increased pulmonary vascular resistance. The process of pulmonary vascular remodeling is accompanied by endothelial dysfunction, activation of fibroblasts and smooth muscle cells, crosstalk between cells within the vascular wall, and recruitment of circulating progenitor cells. Recent findings have reestablished the role of chronic vasoconstriction in the remodeling process. Although the pathology of PAH in the lung is well known, this article is concerned with the cellular and molecular processes involved. In particular we focus on the role of the Rho family guanosine triphosphatases in endothelial function and vasoconstriction. The crosstalk between endothelium and vascular smooth muscle is explored in the context of mutations in the bone morphogenetic protein type II receptor, alterations in angiopoietin-1/TIE2 signaling and the serotonin pathway. We also review the role of voltage-gated K+ (Kv) channels and transient receptor potential channels in the regulation of cytosolic [Ca2+] and [K+], vasoconstriction, proliferation and cell survival. We highlight the importance of the extracellular matrix as an active regulator of cell behavior and phenotype and evaluate the contribution of the glycoprotein tenascin-c as a key mediator of smooth muscle cell growth and survival. Finally, we discuss the origins of a cell type critical to the process of pulmonary vascular remodeling, the myofibroblast, and review the evidence supporting a contribution for the involvement of endothelial-mesenchymal transition and recruitment of circulating mesenchymal progenitor cells.
Subfields: Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/0a5a8aaaf4a9dfd7feee301c7673140766d830b3
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In Molecular Biology
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In Pulmonary and Respiratory Medicine
Citations in the corpus
- ADAPTIVE AND MALADAPTIVE CARDIORESPIRATORY RESPONSES TO CONTINUOUS AND INTERMITTENT HYPOXIA MEDIATED BY HYPOXIA-INDUCIBLE FACTORS 1 AND 2 (2012, background): “Exposure to chronic hypoxia induces functional and structural changes in the endothelial cells, smooth muscle cells, and fibroblasts that make up the intima, media, and adventitia of pulmonary arterial vessels, respectively, and these changes lead to the development of pulmonary arterial hypertensio”