| Background Left Ventricular Hypertrophy(LVH)is an independent risk factor of cardiovascular diseases contributed from hypertension, but detailed mechanisms have remained unidentified and there have been no effective prevention and treatment measures so far. The cardiac myocytes phenotype transition from contractile state to synthetic state has been proved as one of the important pathological bases of LVH. The hypertrophic myocardium shows high quantity oxygen consumption, changes of conduction quality and decreased contractile ability, and these characters will lead to myocardium ischemia, heart failure and arrhythmia. So how to prevent and revert cardiac myocytes hypertrophy and LVH has become a hotly debated global topic. Clinical research has suggested that postmenopausal women have a higher incidence of cardiovascular diseases, compared with the men. This suggests that estrogen plays an important role of the development of cardiovascular deseases. There have been several reports that estrogen can decrease and revert myocardial hypertrophy, at the same time, the clinic data also prove that the estrogen treatment effectively decrease or suspend cardiac hypertrophy. In the past, scientists persist that estrogen signals through ligand regulated transcription factors of the nuclear receptor superfamily. Estrogens binds to classical estrogen nuclear receptors (ER), then activate a serial of transduction signal proteins to elicit biological effects. But scientists find that estrogen can also elicit the rapid non genomic effects in estrogen nuclear receptors ( ERαand ERβ) KO mouse. One of these receptors belongs to an entirely different family of proteins. The G protein coupled and seven transmembrane receptor GPER is now widely recognized as an estrogen receptor,hence its official new acronym GPR30. Then GPR30 becomes more and more popular for its rapid estrogen effects. It has been proved that GPR30 can restrain the development of estrogen associated tumors. There also have been many achievements about cardiovascular, such as reducing blood pression, protecting the myocardium from ischemia reperfusion. But there have been any reports whether estrogen can influence the development of cardiac hypertrophy. This study was therefore designed to observe the effects on cultured cardiac myocytes hypertrophy rats and LVH induced by transverse aorta construction(TAC) in Sprague Dawley (SD), investigated the role of MAPK/ERK pathway in the modulation effects on cardiac myocytes hypertrophy, aimed to clarify the molecular biology mechanism of cardiovascular effects of GPR30,and provided new theoretical evidences and treatment approaches for LVH of hypertrophy.Methods In this study, cultured cardiac myocytes hypertrophy of neonatal SD rats and myocardial hypertrophy induced by transverse aorta constriction (TAC) were used as experimental models. And then immunofluorescence dyeing, HE dyeing, PI Hoechst33258 dyeing, MTT and Western blot were applied to identified:①the expression level of GPR30;②the effects of GPR30 on the norepinephrine induced myocardial cell enlargement of newborn mice;③the effects of GPR30 on the myocardium hypertrophy induced by TAC ;④the effects of GPR30 on pERK expression of myocardiumResults①GPR30 largely expressed in membrane by immunofluorescence dyeing ;②After treatment with 10-4M norepinephrine (NE) for 24h,the surface area of cardiac myocytes (1647.21±155.65㎡) was much higher than that of control group (560.24±109.55㎡)(P>0.01).The surface area of cardiac myocytes was decreased by co intervention with G 1 (specific estrogen membrane receptor GPR30) in a concentration dependent manner. They were 1433.27±153.35㎡,1076.88±199.28㎡,898.74±187.58㎡,1167.34±177.46㎡ in 10pM, 100pM, 1nM, 10nM G 1 group, respectively, which were both significantly lower than that of NE group(P<0.01);③With western blot approach, the expression of anti apoptosis protein Bcl2 in the different concentration groups was significantly higher than that of NE group(P<0.01);④MTT results suggested that G 1 could significantly protect from the injury of cardiac myocytes induced by NE, and the survival rate was both significantly better than NE group(P<0.01);⑤The data of vivo research indicated G 1 could reduce the level of cardiac hypertrophy induced by TAC, compared with TAC group(P<0.01).Conclusions①NE can induce the damage and enlargement of myocardial cell of newborn mice;②The membranous estrogen receptor GPR30 can inhibit NE induced myocardial cell enlargement in the model of new mice in the concentration dependent manner;③GPR30 specific agonist G 1 can significantly inhibit left ventricular hypertrophy;④MAPK/ERK pathway may be one of the signaling pathways participating the effect of GPR30 in LVH. |
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