Current insights on the pathogenesis of pulmonary arterial hypertension

Semin Respir Crit Care Med. 2005 Aug;26(4):355-64. doi: 10.1055/s-2005-916149.


Regardless of the initial trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with pulmonary arterial hypertension are primarily caused by remodeling and thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well as sustained vasoconstriction. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by cellular heterogeneity within each compartment. Indeed, each cell type (endothelial cells, smooth muscle cells, and fibroblasts), as well as inflammatory cells and platelets, may play significant roles in this condition. Recent studies have emphasized the relevance of several mediators in this condition, including prostaglandin-I (2) (prostacyclin), nitric oxide, endothelin-1, angiopoietin-1, 5-hydroxytryptamine (serotonin), cytokines, chemokines, and members of the transforming growth factor beta (TGF-beta) superfamily. Targeting some of these dysfunctional pathways (prostacyclin, nitric oxide, and endothelin-1) has been beneficial in subjects displaying pulmonary arterial hypertension.

Publication types

  • Review

MeSH terms

  • Apoptosis / physiology
  • Endothelium, Vascular / physiopathology
  • Growth Substances / pharmacology
  • Humans
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / physiopathology*
  • Muscle, Smooth, Vascular / physiopathology
  • Neovascularization, Pathologic / physiopathology
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / physiopathology*
  • Thrombosis / physiopathology
  • Vascular Resistance / physiology
  • Vasoconstriction / physiology


  • Growth Substances