The Effect Of Testosterone On The AngiotensinⅡ Induced Proliferation And Collagen Synthesis In Neonatal Rat Cardiac Fibroblasts

Background Myocardial remodeling is the heart adaptability to various stimuli hyperplasia, and is common pathological of coronary heart disease, hypertension, heart failure et al to the end-stage. Myocardial remodeling including heart structure remodeling and electrical remodeling. Myocardial remodeling in early stage is compensatory to cardiac function, enhance the capacity of the contraction of the heart, to keep the normal heart ejection fraction, but with the increase of pressure load and the participation of neurohumoral factors, myocardial remodeling gradually developed to decompensation period, eventually leading to heart failure, arrhythmia, even sudden death. Myocardial fibrosis is the main part of myocardial remodeling, characterized by the myocardial fibroblasts proliferation and collagen synthesis increasing, etc. Myocardial fibrosis can lead to myocardial stiffness increased, compliance reduced, the contraction of cardiac diastolic function limited, so myocardial fibrosis is a independent risk factor of cardiovascular disease. Therefore, effective treatment of myocardial fibrosis is beneficial for coronary heart disease, such as hypertension, heart failure, arrhythmia.Testosterone is a important androgen in the human body, plays an important role in immune function, the growth and development, male sexual desire, physical strength, still can maintain bone density and strength, in addition to many systemsand function of the body also be impacted, such as lipid metabolism, glucose metabolism, inflammation, blood cells proliferation, etc. The presence of testosterone has protective effect on cardiovascular system [7], such as anti-inflammatory, regulating lipid [8], reducing atherosclerosis, dilating vessels, protecting Ang II induced vascular remodeling, etc. But testosterone levels especially the biological effects of testosterone decline gradually along with age. Low testosterone levels serious influence the health of human body, such as muscle strength drops, decreased libido, mood disorders, metabolic syndrome, etc., and the risk of diseases of the cardiovascular system and respiratory system disease will also increase. Testosterone replacement therapy for patients with hypogonadism have a positive therapeutic effect, such as enhance the muscle strength, enhance sexual desire, reduce body fat levels, increased body weight. Studies found that the physiological level of testosterone drugs could reduce the risk of cardiovascular disease, such as improving blood lipid metabolism, diastole of coronary artery. But whether testosterone have an effect on myocardial fibrosis, and what is its specific mechanism? Which is rarely study.Objective To explore the effect and the mechanism of testosterone(T) on proliferation and collagen synthesis of neonatal rat cardiac fibroblast(CF) induced by angiotensin II(Ang II).Methods CF derived from the neonatal rat were cultured with serum-free DMEM culture(control group), 10-6mol·L-1 Ang II(Ang II group), 30nmol·L-1 testosterone(testosterone group), or 30nmol/l testosterone and 10-6mol·L-1 Ang II(testosterone + Ang II group) for 24 h, respectively. Flow cytometry analysis was used to detect cell cycle distribution. VG staining method was used to detect the contents of.collegen,and immunocytochemistry method was used to detect phosphorylated ERK1/2(pERK1/2) expression.Result 1. S phase cell proportion, collagen content and p-ERK1/2 expression level of Ang II group were significantly higher than those of the control group.2. S phase cell proportion and collagen content of testosterone group were found no difference compared with control group, but the p-ERK1/2 expression was higher than control group.3. S phase cell proportion, collagen content and p-ERK1/2 expression level of testosterone + Ang II group were significantly lower than those of Ang II group(S phase cell proportion: FAng II=30.403, Ftestosterone=5.812, Finteraction=18.073, P<0.05; collagen content: FAng II=10.365, Ftestosterone=4.533, Finteraction=42.049, P<0.05, p-ERK1/2 expression level: FAng II=174.762, Ftestosterone=184.828, Finteraction=152.240, P<0.05).Conclusion Testosterone can inhibit CF proliferation and collagen synthesis induced by Ang II, and the mechanism may be related to the inhibition of ERK1/2 activation.