Effects Of Zofenopril On The Expression Of ACE2、Angiotensin Receptors And TGF-β1in Hypertrophic Cardiomyocytes

Part1Objective:To determine whether the ACEI zofenopril can reverse the cardiomyocytes hypertrophy induced by the norepinephrine and how will ACEi zofenopril affect the AT1-TGF-β1signal transduction pathway and the expression of the AT2receptor. Methods:The cultured primary cardiomyocytes were divided into three groops randomly:the normal control groops were routinely cultured;the hypertrophic cardiomyocyte and the zofenopril groops intervened48hours by norepinephrine,then cultured with complete medium and zofenopril added medium,respectively.The extent of cardiomyocytes hypertrophy was researched by testing the levels of expression of natriuretic peptides,which were detected at at the messenger RNA (mRNA) and protein levels.The levels of expression of angiotensin receptors and transforming growth factor-β1(TGF-β1) during cardiomyocytes hypertrophy were investigated at the protein level. Resuts:Compare with the normal control,Administration of norepinephrine to cultured cardiomyocytes caused a up regulation of the expression of angiotensin receptors and TGF-β1in parallel to an increased expression of natriuretic peptides.In response to zofenopril,the expression of angiotensin Ⅱ type1(ATI) receptor and TGF-β1was decreased and the expression of angiotensin Ⅱ type2(AT2) receptor was increased,which were accompanied by the down regulation of the expression of natriuretic peptides. Conclusion:These results suggest that zofenopril may attenuate or reverses cardiomyocytes hypertrophy cultured In vitro via down regulates expression of AT1receptor and TGF-β1,meanwhile up regulates expression of AT2receptor. Part2Objective:To test the effects of zofenopril on the expression of ACE2in hypertrophic cardiomyocytes. Methods:The cultured cardiomyocytes were divided into five groops.the intervention of the normal control groops and the hypertrophic cardiomyocyte groops was the same as part1,.other three groops put different concenrrations of zofenopril,0.5μg/L、5μg/L、50μg/L, or interven for different time,6hours、12hours、24hours,respectively.The expression of ACE2protein was detemined with Western blotting analysis. Results:Zofenopril at the concenrrations of0.5μg/L、5μg/L、50μg/L dose-dependently enhanced the expression of ACE2protein;within0-24h,50μg/L zofenopril increased ACE2protein expression in a time-dependent manner. Conclusion:The reversal effects of zofenopril on cardiomyocytes hypertrophy may be related with its up-regulation of the expression of ACE2protein.