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Review
. 2020 Dec 28;5(12):1244-1260.
doi: 10.1016/j.jacbts.2020.07.011. eCollection 2020 Dec.

Treatment Targets for Right Ventricular Dysfunction in Pulmonary Arterial Hypertension

Sasha Z Prisco  1 , Thenappan Thenappan  1 , Kurt W Prins  1
Affiliations
Review

Treatment Targets for Right Ventricular Dysfunction in Pulmonary Arterial Hypertension

Sasha Z Prisco et al. JACC Basic Transl Sci. .

Abstract

Right ventricle (RV) dysfunction is the strongest predictor of mortality in pulmonary arterial hypertension (PAH), but, at present, there are no therapies directly targeting the failing RV. Although there are shared molecular mechanisms in both RV and left ventricle (LV) dysfunction, there are important differences between the 2 ventricles that may allow for the development of RV-enhancing or RV-directed therapies. In this review, we discuss the current understandings of the dysregulated pathways that promote RV dysfunction, highlight RV-enriched or RV-specific pathways that may be of particular therapeutic value, and summarize recent and ongoing clinical trials that are investigating RV function in PAH. It is hoped that development of RV-targeted therapies will improve quality of life and enhance survival for this deadly disease.

Keywords: FAO, fatty acid oxidation; IPAH, idiopathic pulmonary arterial hypertension; LV, left ventricle/ventricular; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension; RAAS, renin-angiotensin-aldosterone system; RV, right ventricle/ventricular; RVH, right ventricular hypertrophy; SSc-PAH, systemic sclerosis-associated pulmonary arterial hypertension; clinical trials; miRNA/miR, micro-ribonucleic acid; pulmonary arterial hypertension; right ventricle.

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Conflict of interest statement

Dr. Prisco is funded by National Institutes of Health (NIH) grant T32 HL144472, a University of Minnesota Clinical and Translational Science award (NIH UL1 TR0029494), and a University of Minnesota Medical School Academic Investment Educational Program grant. Dr. Prins is funded by NIH K08 HL140100, the Jenesis Award from United Therapeutics, a Lillehei Heart Institute Cardiovascular Seed Grant, and the Cardiovascular Medical Research and Education Fund; and has served as a consultant for Actelion and receives grant funding from United Therapeutics. Dr. Thenappan has served as a consultant for Actelion and Gilead. The content of this article is solely the responsibility of the authors and does not represent the official views of the NIH or any other funding sources. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Developmental, Anatomic, and Functional Differences Between the Right and Left Ventricles ECM = extracellular matrix; ER = estrogen receptor; MHC = myosin heavy chain.
Figure 2
Figure 2
Potentially Targetable Mechanisms of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension HDAC = histone deacetylase; lncRNA = long noncoding RNA; miRNA = microRNA; RAAS = renin-angiotensin-aldosterone system; RV = right ventricle; t-tubule = transverse tubule; Ub = ubiquitin.
Central Illustration
Central Illustration
Potential Treatment Targets for Right Ventricular Dysfunction in Pulmonary Arterial Hypertension HDAC = histone deacetylase; lncRNA = long noncoding RNA; miRNA = microRNA; PAH = pulmonary arterial hypertension; RAAS = renin-angiotensin-aldosterone system; RV = right ventricle; t-tubule = transverse tubule; Ub = ubiquitin.
See this image and copyright information in PMC

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