Current Knowledge and Recent Advances of Right Ventricular Molecular Biology and Metabolism from Congenital Heart Disease to Chronic Pulmonary Hypertension

Abstract

Studies about pulmonary hypertension and congenital heart diseases have introduced the concept of right ventricular remodeling leading these pathologies to a similar outcome: right ventricular failure. However right ventricular remodeling is also a physiological process that enables the normal fetal right ventricle to adapt at birth and gain its adult phenotype. The healthy mature right ventricle is exposed to low pulmonary vascular resistances and is compliant. However, in the setting of chronic pressure overload, as in pulmonary hypertension, or volume overload, as in congenital heart diseases, the right ventricle reverts back to a fetal phenotype to sustain its function. Mechanisms include angiogenic changes and concomitant increased metabolic activity to maintain energy production. Eventually, the remodeled right ventricle cannot resist the increased afterload, leading to right ventricular failure. After comparing the fetal and adult healthy right ventricles, we sought to review the main metabolic and cellular changes occurring in the setting of PH and CHD. Their association with RV function and potential impact on clinical practice will also be discussed.

Figure 1

Main histological patterns of right ventricular remodeling in the setting of chronic pressure overload. Inflammation involving mononuclear cells and cardiomyocytes hypertrophy are observed at the early stage. Reduced capillary density and myocardial fibrosis are associated with right ventricular maladaptive phenotype.

Figure 2

18-Fluorodeoxyglucose Positron Emission Tomography in a control healthy patient (a), in a patient with aortic valve sclerosis (b), and in a chronic thromboembolic pulmonary hypertension patient (CTEPH) (c). Images show 4 chambers views. Control imaging shows no right ventricular uptake, but presence of left ventricular uptake. Picture (b) shows increased glucose uptake localized on the left ventricular free wall and on the interventricular septum in a patient with marked hypertrophy of the left ventricle due to aortic sclerosis.

Figure 3

Right ventricular remodeling in congenital heart disease and pulmonary hypertension. βMHC: β-myosin heavy chain; HIF1α: hypoxia inducible factor 1α; VEGF: vascular endothelial growth factor; SERCA2a: sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a; IVS: interventricular septum; αMHC: α-myosin heavy chain; FAO: fatty acids oxidation; RV-PA coupling: right ventricular-pulmonary arterial coupling; PVR: pulmonary vascular resistances; RV: right ventricular; iPAH: idiopathic pulmonary arterial hypertension; CTEPH: chronic thromboembolic pulmonary hypertension.