Adaptation and remodelling of the pulmonary circulation in pulmonary hypertension

Can J Cardiol. 2015 Apr;31(4):407-15. doi: 10.1016/j.cjca.2014.10.023. Epub 2014 Oct 23.


Pulmonary arterial hypertension (PAH) is characterized by remodelling of pulmonary arteries caused by a proliferation/apoptosis imbalance within the vascular wall. This pathological phenotype seems to be triggered by different environmental stress and injury events such as increased inflammation, DNA damage, and epigenetic deregulation. It appears that one of the first hit to occur is endothelial cells (ECs) injury and apoptosis, which leads to paracrine signalling to other ECs, pulmonary artery smooth muscle cells (PASMCs), and fibroblasts. These signals promote a phenotypic change of surviving ECs by disturbing different signalling pathways leading to sustained vasoconstriction, proproliferative and antiapoptotic phenotype, deregulated angiogenesis, and formation of plexiform lesions. EC signalling also recruits proinflammatory cells, leading to pulmonary infiltration of lymphocytes, macrophages, and dendritic cells, sustaining the inflammatory environment and autoimmune response. Finally, EC signalling promotes proliferative and antiapoptotic PAH-PASMC phenotypes, which acquire migratory capacities, resulting in increased vascular wall thickness and muscularization of small pulmonary arterioles. Adaptation and remodelling of pulmonary circulation also involves epigenetic components, such as microRNA deregulation, DNA methylation, and histone modification. This review will focus on the different cellular and epigenetic aspects including EC stress response, molecular mechanisms contributing to PAH-PASMC and PAEC proliferation and resistance to apoptosis, as well as epigenetic control involved in adaptation and remodelling of the pulmonary circulation in PAH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / physiology*
  • Humans
  • Hypertension, Pulmonary / physiopathology*
  • Pulmonary Artery / physiopathology*
  • Pulmonary Circulation / physiology*
  • Pulmonary Wedge Pressure*
  • Vascular Remodeling / physiology*