Table 1.
Summary of key findings in the right ventricle during rest, hypertrophy and failure.
| Pathways | Effect of RV Hypertrophy and Failure | Significance in the RV | LV Hypertrophy and Failure |
|---|---|---|---|
| Metabolic adaptation | ↓ Fatty acid binding protein (non-stressed state) ↑ Glycolysis ↓ Mitochondrial complex 1, III, IV. ↓ Resting mitochondrial membrane potential; hyperpolarized with hypertrophy. ↓ Mitochondrial DNA with failure in CHD. |
↓ Energy production | - FABP - Resting mitochondrial membrane potential |
| Oxidative stress | ↑ Hif-1α activation and complex II-mediated ROS production. Antioxidant enzymes (SOD, GPX) are not activated with hypertrophy ↓ PGC1α |
↑ Mitochondrial ROS production | ↑ NADPH oxidase mediated ROS production ↑ Antioxidant enzyme activity (SOD, GPX) with hypertrophy NADPH oxidase mediated ROS production |
| Electrical remodeling | ↓ Kv channel expression, prolonging the action potential duration and QT interval | ↑ Risk of arrhythmias | No change in action potential duration; Increased membrane capacitance |
| Angiogenesis | ↓ Microvascular bed ↓ Angiogenic response |
↑ Susceptibility to ischemia | ↑ Microvascular bed and angiogenic response with hypertrophy. |
| Response to hypoxia | ↑ Glycolysis | ↓ Energy production | ↑ Glycolysis |
| Adrenergic Receptors | ↓ β1-, α1- and DA1 receptors, ↓ cAMP levels and ↑ GRK2 activity ↑ Coupling of β2 receptors to Gs ↓ Myofilament Ca2+ sensitivity through phosphorylation of MLCK (non stress) |
↓ Inotropic response ↑ β2-receptor mediated inotropy and lusitropy56 Negative α1-signaling (non stress) switches to positive (failure). |
Positive α1-signaling (non stress) due to ↑ myofilament Ca2+ sensitivity. |
| RAAS MicroRNAs | RAAS activation Non-cardiomyocyte origin of some miRs Defect in miR-126/VEGF pathway. |
Hypertrophy Paracrine effect of cardiomyocytes ↓ Angiogenesis |
RAAS activation Cardiomyocyte origin of miR-34a |
FABP – fatty acid binding protein, CHD - congenital heart disease, SOD - superoxide dismutase, GPX - glutathione peroxidase, GRK - G protein-coupled receptor kinase, MLCK - myosin light chain, RAAS - renin-angiotensin-aldosterone system