Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension

Prog Cardiovasc Dis. 2002 Nov-Dec;45(3):173-202. doi: 10.1053/pcad.2002.130041.


Clinical pulmonary hypertension is characterized by a sustained elevation in pulmonary arterial pressure. Pulmonary vascular remodeling involves structural changes in the normal architecture of the walls of pulmonary arteries. The process of vascular remodeling can occur as a primary response to injury, or stimulus such as hypoxia, within the resistance vessels of the lung. Alternatively, the changes seen in more proximal vessels may arise secondary to a sustained increase in intravascular pressure. To withstand the chronic increase in intraluminal pressure, the vessel wall becomes thickened and stronger. This "armouring" of the vessel wall with extra-smooth muscle and extracellular matrix leads to a decrease in lumen diameter and reduced capacity for vasodilatation. This maladaptive response results in increased pulmonary vascular resistance and consequently, sustained pulmonary hypertension. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by the finding that cellular heterogeneity exists within the traditional compartments of the vascular wall: intima, media, and adventitia. In addition, the developmental stage of the organism greatly modifies the response of the pulmonary circulation to injury. This review focuses on the latest advances in our knowledge of these processes as they relate to specific forms of pulmonary hypertension and particularly in the light of recent genetic studies that have identified specific pathways involved in the pathogenesis of severe pulmonary hypertension.

Publication types

  • Review

MeSH terms

  • Angiotensin II / metabolism
  • Animals
  • Apoptosis
  • Bone Morphogenetic Proteins / metabolism
  • Cell Cycle
  • Endothelial Growth Factors / metabolism
  • Endothelin-1 / metabolism
  • Epoprostenol / metabolism
  • Growth Substances / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1
  • Humans
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / pathology*
  • Hypertension, Pulmonary / physiopathology
  • Hypoxia / complications
  • Hypoxia / metabolism
  • Inflammation Mediators / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lymphokines / metabolism
  • Matrix Metalloproteinases / metabolism
  • Membrane Proteins
  • Nitric Oxide / metabolism
  • Pancreatic Elastase / metabolism
  • Pulmonary Circulation
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Tenascin / metabolism
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Bone Morphogenetic Proteins
  • Endothelial Growth Factors
  • Endothelin-1
  • Growth Substances
  • Inflammation Mediators
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Membrane Proteins
  • Reactive Oxygen Species
  • Tenascin
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Angiotensin II
  • Nitric Oxide
  • Epoprostenol
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Pancreatic Elastase
  • Matrix Metalloproteinases