New mechanisms of pulmonary arterial hypertension: Role of Ca 2+signaling

Frank K. Kuhr, Kimberly A. Smith, Michael Y. Song, Irena Levitan, Jason X.J. Yuan

Research output: Contribution to journalReview articlepeer-review

128 Scopus citations


Pulmonary arterial hypertension (PAH) is a severe and progressive disease that usually culminates in right heart failure and death if left untreated. Although there have been substantial improvements in our understanding and significant advances in the management of this disease, there is a grim prognosis for patients in the advanced stages of PAH. A major cause of PAH is increased pulmonary vascular resistance, which results from sustained vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular stiffness. In addition to other signal transduction pathways, Ca 2+ signaling in pulmonary artery smooth muscle cells (PASMCs) plays a central role in the development and progression of PAH because of its involvement in both vasoconstriction, through its pivotal effect of PASMC contraction, and vascular remodeling, through its stimulatory effect on PASMC proliferation. Altered expression, function, and regulation of ion channels and transporters in PASMCs contribute to an increased cytosolic Ca 2+ concentration and enhanced Ca 2+ signaling in patients with PAH. This review will focus on the potential pathogenic role of Ca 2+ mobilization, regulation, and signaling in the development and progression of PAH.

Original languageEnglish (US)
Pages (from-to)H1546-H1562
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number8
StatePublished - Apr 15 2012
Externally publishedYes


  • Calcium channel
  • Calcium regulation
  • Canonical transient receptor potential channel
  • Vascular remodeling
  • Vasoconstriction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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