Right ventricular adaptation and failure in pulmonary arterial hypertension

John J. Ryan, Jessica Huston, Shelby Kutty, Nathan D. Hatton, Lindsay Bowman, Lian Tian, Julia E. Herr, Amer M. Johri, Stephen L. Archer

Research output: Contribution to journalReview articlepeer-review

85 Scopus citations


Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy, characterized by excess proliferation, apoptosis resistance, inflammation, fibrosis, and vasoconstriction. Although PAH therapies target some of these vascular abnormalities (primarily vasoconstriction), most do not directly benefit the right ventricle (RV). This is suboptimal because a patient's functional state and prognosis are largely determined by the success of the adaptation of the RV to the increased afterload. The RV initially hypertrophies but might ultimately decompensate, becoming dilated, hypokinetic, and fibrotic. A number of pathophysiologic abnormalities have been identified in the PAH RV, including: ischemia and hibernation (partially reflecting RV capillary rarefaction), autonomic activation (due to G protein receptor kinase 2-mediated downregulation and desensitization of β-adrenergic receptors), mitochondrial-metabolic abnormalities (notably increased uncoupled glycolysis and glutaminolysis), and fibrosis. Many RV abnormalities are detectable using molecular imaging and might serve as biomarkers. Some molecular pathways, such as those regulating angiogenesis, metabolism, and mitochondrial dynamics, are similarly deranged in the RV and pulmonary vasculature, offering the possibility of therapies that treat the RV and pulmonary circulation. An important paradigm in PAH is that the RV and pulmonary circulation constitute a unified cardiopulmonary unit. Clinical trials of PAH pharmacotherapies should assess both components of the cardiopulmonary unit.

Original languageEnglish (US)
Pages (from-to)391-406
Number of pages16
JournalCanadian Journal of Cardiology
Issue number4
StatePublished - Apr 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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