| Background Left ventricular hypertrophy (LVH) is regarded as a strong independent risk factor for the morbidity and mortality of essential hypertension (EH). Nowdays the reversal of LVH is one of main targets for the treatment of EH. Besides cardiomyocytes hypertrophy, the pathological basis of left ventricular hypertrophy shows cardiac fibroblasts (CFs) proliferation and excessive extracellular matrix (ECM) protein accumulation, which leads to myocardial fibrosis. Hypertensive myocardial fibrosis has been shown to facilitate ventricular dysfunction, diminished coronary reserve and ventricular arrhythmias that adversely affect the clinical outcome of hypertensive patients.It has been approved that humoral factors, not hemodynamic factors, are important in the formation of myocardial fibrosis. Epidemiological surveys have shown that the mortality of male hypertensive patients with LVH is higher than that of female hypertensive patients with LVH, which suggests that gender is close related to the clinical prognosis of hypertensive patients with LVH. Clinical data has proved that transdermal 17beta-estradiol, combined with standard antihypertensive therapy, may contribute in the reduction of left ventricular mass in hypertensive postmenopausal women, which suggests that 17beta-estradiol may reduce LVH. Till now, the role of estrogen in the pathogenesis of LVH associated with hypertension has not been clearly defined. 17beta-estradiol has been proved to inhibit CFs prolifertion and collagen synthesis; however, whether17beta-estradiol is involed in the degradation of ECM is still obscure. The aim of this study was to investigate the effects of 17beta-estradiol on matrix metalloproteinases and tissue inhibitors of metalloproteinases (MMPs/TIMPs) in the adult rat CFs in hope of finding an new way for exploring the etiology and treatment of LVH associated with hypertension.Methods Male and female adult Sprague-Dawley (SD) rat CFs were isolated and cultured by collagenase-trypsin digestion and selective plating technique. Gelatinase activity was measured by gelatinase zymography. MMP-1, MMP-2, TIMP-1, TIMP-2 mRNA levels were detected by reversed transcription-polymerase chain reaction (RT-PCR). MMP-1 and TIMP-1 protein levels were measured by western blot.Results The results showed that : (l)17beta-estradiol increased gelatinase activity in a concentation dependent manner in female and male rat CFs supernatant, respectively. In female rat CFs supernatant, 10-10-10-6M 17beta-estradiol increased gelatinase activity by (42±11)%, (61±13)%, (66± 14)%, (83±17)% and (90±18)% compared with control (P<0.01, respectively). In male rat CFs supernatant, 10-10-10-6M 17beta-estradiol increased gelatinase activity by (25±4)%, (34±5)%, (83±6)%, (95±6)% and (110±10)% compared with control (P<0.01, respectively). (2) 17beta-estradiol upregulated MMP-1 mRNA levels in a concentration dependent manner in female and male rat CFs, respectively. In female rat CFs, 10-8M-10-6M 17beta-estradiol significantly upregulated MMP-1 mRNA levels in comparison to control (0.34± 0.03, 0.38±0.04, 0.42±0.04 vs 0.23±0.03) (P<0.05, P<0.01 and P<0.01, respectively); besides, 10-6M activator protein-1 (AP-1) inhibitor curcumin significantly decreased MMP-1 mRNA level in female rat CFs induced by 10-7M 17beta-estradiol (0.25±0.03 vs 0.38±0.04) (P<0.01). In male rat CFs, 10-8M-10-6M 17beta-estradiol significantly upregulated MMP-1 mRNA levels in comparison to control (0.32±0.03, 0.39±0.05, 0.45±0.04 vs 0.23±0.02)(P<0.05, P<0.01 and P<0.01, respectively); moreover, 10-6M curcumin significantly decreased MMP-1 mRNA level in male rat CFs induced by 10-7M 17beta-estradiol (0.24±0.04 vs 0.39±0.05) (P<0.01). There seemed to be no significant difference in the effects of 17beta-estradiol and curcumin on MMP-1 mRNA levels in female and male rat CFs. (3) 17beta-estradiol upregulated MMP-2 mRNA levels in a concentration dependent manner in female and male rat CFs, respectively. In female rat CFs, 10-10M-10-6M 17beta-estradiol...
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