Converging Paths of Pulmonary Arterial Hypertension and Cellular Senescence

Am J Respir Cell Mol Biol. 2019 Jul;61(1):11-20. doi: 10.1165/rcmb.2018-0329TR.

Abstract

Cellular senescence is recognized as a crucial contributor to the pathobiology of various degenerative and cardiovascular diseases, such as idiopathic pulmonary fibrosis and atherosclerosis. We describe the potential link between cellular senescence and the degenerative character of neointimal pulmonary vascular disease in pulmonary arterial hypertension (PAH). Senescence markers have been described in remodeled pulmonary arteries, and PAH and senescence share common triggers and pathogenic pathways, such as transforming growth factor-β/bone morphogenetic protein and TNF-α. In addition, interventions that target a senescence phenotype also target pulmonary vascular remodeling in vivo. These data provide a basis for further exploration of the role of senescence in the pathobiology of PAH and for preclinical trials with a senolytic class of drugs.

Keywords: cellular senescence; pulmonary arterial hypertension; senescence-associated secretory phenotype; senolysis; vascular remodeling.

Publication types

  • Editorial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / pathology
  • Animals
  • Cellular Senescence*
  • Humans
  • Janus Kinases / metabolism
  • Lung / pathology
  • Pulmonary Arterial Hypertension / pathology*
  • STAT Transcription Factors / metabolism
  • Signal Transduction*

Substances

  • STAT Transcription Factors
  • Janus Kinases