Table 3.
Anti-remodeling effects of GPER activation in cardiac tissue and cells.
| Species or cells | Models/Strains | G1 treatment | Effects of intervention |
|---|---|---|---|
| Rat | mRen2.Lewis rats/OVX (25) | s.c., 50 μg/kg/day, for 2 weeks |
Limited OVX-induced ↑ LV filling pressure, LV mass, wall thickness, interstitial collagen deposition, and cardiac ANF and BNP mRNA levels |
| mRen2.Lewis rats/high salt diet (65) | s.c., 40 nmol/kg/hr, for 2 weeks | Improved myocardial relaxation and reduced cardiac myocyte hypertrophy and wall thickness | |
| F344BN old-aged rats/OVX (24) | s.c. 100 μg/kg/day, for 8 weeks | Reversed adverse effects of age and estrogen loss on myocardial relaxation and interstitial collagen deposition | |
| Wistar rats/OVX + monocrotaline-induced pulmonary hypertension (20) | s.c., 400 μg/kg/day, for 14 days after the onset of disease | Limited adverse effects of pulmonary hypertension on RV interstitial fibrosis, RV free wall thickening, and LV diastolic function | |
| Wistar rats/myocardial infarction (121) | 50 μg/kg per day, gastric gavage, for 4 weeks | Attenuated LV hypertrophy, assessed by cardiomyocyte size, to an extent similar to E2 | |
| Wistar rats/OVX and diabetes mellitus (122) | i.p. injection, 50 μg/kg, every 4 days for 4 weeks |
Improved cardiac weight, atherogenic and cardiovascular risk indices; meanwhile GPER antagonism with G15 exacerbated cardiac weight and atherogenic indices | |
| SD rats/OVX + ISO-induced heart failure (123) | s.c.,120 μg/kg·d, for 14 days | Decreased cardiac BNP, reduced cardiac fibrosis, and enhanced contraction | |
| Mouse | C57BL/6 mice/OVX & myocardial infarction (124) | i.p. injection, 35 μg/kg/d, for 4 weeks |
Reduced myocardial fibrosis and infarct area |
| Ramp3+/+ and Ramp3−/− (125) | s.c., 0.1 mg/kg/day, for 40 days | Reduced perivascular fibrosis and cardiomyocyte area in RenTgMK/Ramp3+/+ male mice | |
| Neonatal rat cardiomyocytes | ET-1 (100 nmol/l) for 48 h (126) | 10 nmol/l for 48 h | Abolished hypertrophic actions of ET-1, which was reversed by G15; siRNA silencing of GPER inhibited antihypertrophic effect of E2 |
| 100 nM of Ang II for 24 h (127) | 1,000 nM for 24 h | Attenuated Ang II-induced cardiomyocyte hypertrophy and downregulated mRNA levels of ANF and BNP |
|
| H9c2 cardiomyocytes | Ang II (10−7M) for 24 h (25) | 10−7 M for 24 h | Inhibited Ang II-induced hypertrophy, evidenced by reductions in cell size, protein content per cell, and ANF mRNA levels; G15 inhibited protective effects of G1 or E2 |
| Adult rat cardiac fibroblasts | Growth medium with 10% FBS (57) | 0.01–10 μM for 24 h | Inhibited proliferation of rat cardiac fibroblasts |
ANF, atrial natriuretic factor; Ang II, angiotensin II; BNP, brain natriuretic peptide; E2, estradiol; ET-1, endothelin-1; FBS, fetal bovine serum; i.p., intraperitoneal; ISO, isoproterenol; LV, left ventricular; OVX, ovariectomized; RV, right ventricular; s.c., subcutaneous; μg, micrograms; SD, Sprague Dawley.