Cellular and Molecular Basis of Pulmonary Arterial Hypertension

Nicholas W. Morrell, Serge Adnot, Stephen L. Archer, Jocelyn Dupuis, Peter Lloyd Jones, Margaret R. MacLean, Ivan F. McMurtry, Kurt R. Stenmark, Patricia A. Thistlethwaite, Norbert Weissmann, Jason Yuan, E. Kenneth Weir

Research output: Contribution to journalArticle

528 Citations (Scopus)

Abstract

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+ 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.

Original languageEnglish (US)
JournalJournal of the American College of Cardiology
Volume54
Issue number1 SUPPL. 1
DOIs
StatePublished - Jun 30 2009
Externally publishedYes

Fingerprint

Pulmonary Hypertension
Vasoconstriction
Lung
Smooth Muscle Myocytes
Cell Survival
Type II Bone Morphogenetic Protein Receptors
Angiopoietin-1
Transient Receptor Potential Channels
Voltage-Gated Potassium Channels
Tenascin
Myofibroblasts
Guanosine
Mesenchymal Stromal Cells
Vascular Smooth Muscle
Vascular Resistance
Endothelium
Extracellular Matrix
Blood Vessels
Serotonin
Glycoproteins

Keywords

  • cellular
  • molecular basis
  • pulmonary arterial hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Morrell, N. W., Adnot, S., Archer, S. L., Dupuis, J., Lloyd Jones, P., MacLean, M. R., ... Weir, E. K. (2009). Cellular and Molecular Basis of Pulmonary Arterial Hypertension. Journal of the American College of Cardiology, 54(1 SUPPL. 1). https://doi.org/10.1016/j.jacc.2009.04.018

Cellular and Molecular Basis of Pulmonary Arterial Hypertension. / Morrell, Nicholas W.; Adnot, Serge; Archer, Stephen L.; Dupuis, Jocelyn; Lloyd Jones, Peter; MacLean, Margaret R.; McMurtry, Ivan F.; Stenmark, Kurt R.; Thistlethwaite, Patricia A.; Weissmann, Norbert; Yuan, Jason; Weir, E. Kenneth.

In: Journal of the American College of Cardiology, Vol. 54, No. 1 SUPPL. 1, 30.06.2009.

Research output: Contribution to journalArticle

Morrell, NW, Adnot, S, Archer, SL, Dupuis, J, Lloyd Jones, P, MacLean, MR, McMurtry, IF, Stenmark, KR, Thistlethwaite, PA, Weissmann, N, Yuan, J & Weir, EK 2009, 'Cellular and Molecular Basis of Pulmonary Arterial Hypertension', Journal of the American College of Cardiology, vol. 54, no. 1 SUPPL. 1. https://doi.org/10.1016/j.jacc.2009.04.018
Morrell NW, Adnot S, Archer SL, Dupuis J, Lloyd Jones P, MacLean MR et al. Cellular and Molecular Basis of Pulmonary Arterial Hypertension. Journal of the American College of Cardiology. 2009 Jun 30;54(1 SUPPL. 1). https://doi.org/10.1016/j.jacc.2009.04.018
Morrell, Nicholas W. ; Adnot, Serge ; Archer, Stephen L. ; Dupuis, Jocelyn ; Lloyd Jones, Peter ; MacLean, Margaret R. ; McMurtry, Ivan F. ; Stenmark, Kurt R. ; Thistlethwaite, Patricia A. ; Weissmann, Norbert ; Yuan, Jason ; Weir, E. Kenneth. / Cellular and Molecular Basis of Pulmonary Arterial Hypertension. In: Journal of the American College of Cardiology. 2009 ; Vol. 54, No. 1 SUPPL. 1.
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