Table 2.
Studies evaluating RV vasculature in maladaptive RV hypertrophy
| Reference | Maladaptive Model(s) | How Was Maladaptive Remodeling Defined? | RV Parameters Evaluated | Main Results |
|---|---|---|---|---|
| Partovian et al. (117) | Rats: MCT (60 mg/kg, 1–30 days) | DNE | RVSP, RVH, RV function by right heart catheterization | ↓RV VEGF mRNA |
| Ruiter et al. (131) | Rats: MCT (60 mg/kg, 4 wk) | ↓cardiac output, ↓body weight | RVSP, RVH, RV function by right heart catheterization, endurance testing and echocardiography | ↓RV capillary density |
| Human PAH RVs | ||||
| Piao et al. (122) | Rats: MCT (60 mg/kg, 4 wk) | RVH, more severe ischemia, autonomic remodeling, ↓TAPSE, ↓RV dysfunction compared with PAB | RVSP, RVH RV function by echocardiography, right heart catheterization thermodilution, exercise capacity Contractile function by Langendorff | ↓VEGFA |
| Human PAH and Scleroderma-PAH RVs | ↓RV capillarization | |||
| ↓Coronary blood flow | ||||
| ↓Capillarization in human scleroderma-PAH RVs | ||||
| Sutendra et al. (151) | Rats: MCT (60 mg/kg, 5–6 wk) | ↓RVSP and ↓cardiac output but ↑mean pulmonary artery pressure, continued RV remodeling, development of ascites, weight loss, fluid retention | RVH, RVSP, RV function by right heart catheterization, echocardiograph | Inhibition of HIF1 |
| Activation of p53 | ||||
| ↓VEGFA, ↓SDF1 | ||||
| ↓RV angiogenesis compared with compensated RVs | ||||
| Potus et al. (124) | Rats: MCT (60 mg/kg, 3–4 wk) | Rats-↑RV size, ↑RV end-diastolic pressure increased, ↓TAPSE, ↓stroke volume, and ↓cardiac output | Rats-RVSP, RVH, RV function by pressure-volume loops, echocardiograph, endurance testing Humans-Echocardiography, right heart catheterization | ↓mIR-126 |
| Human decompensated RVs and RV ECs | ↓SPRED1 | |||
| ↓ RV angiogenesis | ||||
| ↓Capillary density | ||||
| Humans-↓TAPSE, RV dilation | Functionally impaired ECs | |||
| Drake et al. (43) | Rats: SuHx | ↓cardiac output, ↓TAPSE, paradoxical movement of interventricular septum, pericardial fluid, ↓capillaries, ↑fibrosis | DNE | ↓Apelin protein |
| Rats: PABCu2+ (6 wk) | ↓VEGF-A, IGF1, apelin and Ang1 mRNA | |||
| Bogaard et al. (14) | Rats: SuHx | RVH, pericardial fluid, paradox movement of septum, RV dilation, ↓TAPSE, ↓cardiac output | RVSP, RVH, RV function by echocardiography, pressure-volume loops, thermodilution | ↓Capillary density |
| ↓VEGFA mRNA and protein | ||||
| Uncoupling of HIF1 and VEGF | ||||
| Bogaard et al. (15) | Rats: SuHx + Carvedilol | RVH, pericardial fluid, paradox movement of septum, RV dilation, ↓TAPSE, ↓cardiac output | RVSP, RVH, RV function by echocardiography, exercise endurance, hemodynamic assessment | Carvedilol treated rats had ↑capillary density |
| Graham et al. (61) | Human PH RVs | DNE | DNE | Stereological assessment of human revealed RVs had ↑capillary length and volume |
| Matori et al. (100) | Rats: MCT (60 mg/kg 30 days +Genistein last 10days) | ↓RV ejection fraction | RVSP, RVH, RV function by right heart catheterization, echocardiograph | ↓ RV capillarization in MCT rats, Genistein treatment ↑capillarization |
| Alzoubi et al. (5) | Rats: SuHx + 5 wk DHEA | ↓TAPSE | RVSP, RVH, RV function by right heart catheterization, echocardiograph | ↓RV capillarization in SuHx rats, treatment with DHEA ↑ RV capillarization |
| ↓Cardiac Index | ||||
| Handoko et al. (64) | Rats: MCT (60 mg/kg, last 4 wk exercise training as able) | ↓cardiac output, | RVSP, RVH, RV function by right heart catheterization, endurance testing and echocardiography | Exercise training ↓capillarization |
| ↓body weight | ||||
| van Albada (168) | Rats: aortocaval shunt + MCT (60 mg/kg + iloprost or aspirin for 30 days) | DNE | Mean pulmonary artery pressure, RVSP, RVH, RV function by right heart catheterization and echocardiograph | MCT ↓capillary to cardiomyocyte ratio |
| Prostacyclin treatment ↑ capillary to cardiomyocyte ratio |
Studies using human tissue are in boldface. Ang1, angiopoietin-1; DNE, did not evaluate adaptive vs. malaptive remodeling; ↑, increase; ↓, decrease; DHEA, dehydroepiandrosterone; EC, endothelial cell; HIF1, hypoxia-inducible factor 1; Hif1α+/−, Hif1α heterozygous knockout mouse; Hx, chronic hypoxia; IGF1, insulin-like growth factor 1; MCT, monocrotaline; PAB, pulmonary artery banding; PABCu2+, pulmonary artery banding + copper depleted diet; RVH, right ventricular hypertrophy; RVSP, right ventricular systolic pressure; SDF1, stromal derived factor 1; SuHx, Sugen5416 + hypoxia; TAPSE, tricuspid annular plane systolic excursion; TSA, trichostatin A; VEGF, vascular endothelial growth factor; VPA, valproic acid.