Table 5.
Therapeutic approaches to improve RV function in PH involving connexins.
| Species | Model | Result | Reference |
|---|---|---|---|
| Mouse | PAB or sham surgery, rhACE2 (1.8 mg/kg/d) or vehicle on post-op day 2, analysis 2 w after surgery | rhACE2: EF↑, RVH ↓; normalized the decreased Cx37 mRNA after PAB | [92] |
| Human | PAECs from PH patients treated with 1 µM MC1568 for 24 h | MC1568: normalized the decreased Cx37 and Cx40 expression | [67] |
| Rat | MCT (60 mg/kg) or saline, MC1568 (50 mg/kg) or saline daily | MC1568: RVSP ↓, RVH ↓ | |
| Rat | MCT (60 mg/kg) or saline, after 3 w: intra-tracheal delivery of aerosolized AAV1.SERCA2a or no treatment, analysis after additional 3–4 w | AAV1.SERCA2a: reversal of electrophysiological remodeling; RV: normalized amounts of Cx43 mRNA and protein; normalized amounts of SERCA2a, of ion channels | [74] |
| Rat | MCT (60 mg/kg), MCT + nicorandil (5 mg/kg/d), MCT + colchicine (1 mg/kg/d), MCT + nicorandil + colchicine, analysis after 90 d | Compared to MCT alone: all groups showed RVSP ↓, RVH ↓, normalization of Cx43 protein | [84] |
| Rat | MCT (75 mg/kg), MCT + cilostazol (20 mg/kg/d, day 28–90) or saline, analysis after 90 d | Cilostazol: RVSP ↓, RVH ↓, Cx43 protein in RV and lung ↑ | [86] |
| Rat | MCT (65 mg/kg), MCT + sildenafil (25 mg/kg/d, Day 21–90) or saline, analysis after 90 d |
Sildenafil: RVSP ↓, RV weight ↓, Cx43 protein in RV ↑ | [85] |
| Rat | MCT (60 mg/kg), MCT + bosentan (300 mg/kg/d, starting 2 w after MCT, or vehicle, analysis 5 w after MCT | Bosentan: RVSP ↓, RV/LV thickness ratio unchanged, prevention of Cx43 lateralization | [90] |
| Rat | MCT (60 mg/kg), MCT+ Carbenoxolone (20 mg/kg/d), analysis after 4 w | Carbenoxolone: RVH ↓; Cx43-expressing CD4+ and CD8+ cells in lungs of MCT-treated rats | [100] |
EF: ejection fraction; HF: heart failure; MCT: monocrotaline; LV: left ventricle; PAEC: pulmonary arterial endothelial cells; PH: pulmonary hypertension; rhACE2: recombinant human angiotensin-converting enzyme 2; RVH: right ventricular hypertrophy; RVSP: right ventricular systolic pressure; SERCA2a: sarcoplasmic reticulum calcium ATPase 2a; ↑: increased; ↓: decreased.