MRI: One-Stop Shop for the Comprehensive Assessment of Pulmonary Arterial Hypertension?

Abstract

Pulmonary arterial hypertension (PAH) is a complex disease that affects the right-sided circulation, including the right ventricle (RV) and the pulmonary vasculature. An obliterative remodeling in the vascular wall, characterized by increased cellular proliferation and suppressed apoptosis, 1 Michelakis ED Spatio-temporal diversity of apoptosis within the vascular wall in pulmonary arterial hypertension: heterogeneous BMP signaling may have therapeutic implications. Circ Res. 2006; 98: 172-175 Crossref PubMed Scopus (60) Google Scholar leads to occlusion of pulmonary arteries (PAs), increased RV afterload, RV failure, and premature death. Emerging therapies target the proliferation/apoptosis of vascular cells, rather than vascular tone, that characterized PAH therapeutics during the past 50 years. 2 Zhao YD Courtman DW Deng Y et al. Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res. 2005; 96: 442-450 Crossref PubMed Scopus (406) Google Scholar 3 Cowan KN Heilbut A Humpl T et al. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med. 2000; 6: 698-702 Crossref PubMed Scopus (326) Google Scholar 4 McMurtry MS Archer SL Altieri DC et al. Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest. 2005; 115: 1479-1491 Crossref PubMed Scopus (318) Google Scholar 5 McMurtry MS Bonnet S Wu X et al. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res. 2004; 95: 830-840 Crossref PubMed Scopus (380) Google Scholar Despite the progress in the vascular biology of PAH, there is an impressive relative lack of studies of the RV in both animals and humans. This is despite the recognition that both the morbidity and mortality of PAH patients are largely driven by the function of the RV. 6 Voelkel NF Quaife RA Leinwand LA et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006; 114: 1883-1891 Crossref PubMed Scopus (969) Google Scholar Traditionally, studies of the heart focus on the systemic circulation and the left ventricle (LV), and effects on the RV are merely extrapolated from the LV. However, there is recent recognition that there are several fundamental differences between the RV and LV, including their responses to increased afterload and their perfusion, among others. 6 Voelkel NF Quaife RA Leinwand LA et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006; 114: 1883-1891 Crossref PubMed Scopus (969) Google Scholar Intriguingly, the two ventricles have a different embryologic origin. 7 Zaffran S Kelly RG Meilhac SM et al. Right ventricular myocardium derives from the anterior heart field. Circ Res. 2004; 95: 261-268 Crossref PubMed Scopus (297) Google Scholar Accordingly, there is now a call for further research regarding the RV with an RV-specific request for proposal by the National Institutes of Health (NIH) as well as an NIH subcommittee taskforce for the promotion of research and understanding of RV biology. 6 Voelkel NF Quaife RA Leinwand LA et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006; 114: 1883-1891 Crossref PubMed Scopus (969) Google Scholar