title: Right ventricular adaptation and failure in pulmonary arterial hypertension.
abstract: 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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
authors.affiliation: Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Huston
authors.affiliation: Pediatric Cardiology, University of Nebraska Medical Center, Children's Hospital and Medical Center, Omaha, Nebraska, USA.
authors.forename: Shelby
authors.initials: S
authors.lastname: Kutty
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Hatton
authors.affiliation: Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Bowman
authors.affiliation: Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Lian
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Herr
authors.affiliation: Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Amer M
authors.initials: AM
authors.lastname: Johri
authors.affiliation: Department of Medicine, Queen's University, Kingston, Ontario, Canada. Electronic address: stephen.archer@queensu.ca.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Archer
mesh_terms: D000222:Adaptation, Physiological; D003952:Diagnostic Imaging; D018450:Disease Progression; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D018497:Ventricular Dysfunction, Right / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D016278:Ventricular Function, Right / Q000502:physiology*
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