Effects Of Short-chain Acyl-coA Dehydrogenase On Cardiac Fibrosis

Objective Short-chain acyl-Co A dehydrogenase(SCAD)is the first enzyme of fatty acid β-oxidation,which caytalyses the short-chain acyl-Co A.SCAD plays an important role in cardiac hypertrophy and cardiomyocyte apoptosis in previous study.However,the effect of SCAD on cardiac fibrosis remains unknown.We aimed to determine the role of SCAD on cardiac fibrosis.We also investigate PPARα regulations of SCAD on cardiac fibrosis in order to explore a new target to prevent cardiac fibrosis.Methods1.Animal model of cardiac fibrosis was induced by spontaneously hypertensive rats(SHR),the effect of swimming training on SHR was observed.The expression of SCAD and fibrotic factors were measured.The ATP content and free fatty acid were also investigated.2.Primary cardiac fibroblasts were harvested from Animal model of cardiac fibrosis induced by SHR.The expression of SCAD and fibrotic factors were measured.The ATP content and free fatty acid were also investigated.The effect of swimming training on SHR was also observed.3.The primary CFs treated with angiotensin(Ang II)were used as the model of cardiac fibrosis.The expression of SCAD was measured.The optimal interfrence sequence 1186 was treated cells for 72 h,then we detected the epression of SCAD,then the expression of collagen I,collagen III and a-SMA were detected.At the same time,ATP content and free fatty acid were also investigated.4.Cells were pretreated with PPARα activator fenofibrate for 30 min,then stimulated with t BHP or si RNA 1186.Expression of SCAD and PPARα,collagen I,collagen III and a-SMA,the ATP content and free fatty acid were detected.Results1.The expression and enzyme activities of SCAD were significantly decreased in SHR compared with wistar rats.Furthermore,ATP content was obviously decreased.Meanwhile,swim training may obviously ameliorate the cardiac fibrosis in SHR by increasing the expression of SCAD,with the increased fatty acid oxidation level and decreaed fibrotic factors.2.The CFs showed increased rates of proliferation,the expression of a-SMA,collagen I and collagen III were significantly increased in CFs of SHR compared with CFs of wistar rats.Meanwhile,the expression and enzyme activity of SCAD were significantly decreased in CFs of SHR,which was consistent with the changes in the left ventricles of SHR.Furthermore,ATP content was obviously decreased.However,swim training may obviously ameliorate the cardiac fibrosis in CFs of SHR by increasing the expression of SCAD,with the increased fatty acid oxidation level and decreaed fibrotic factors.3.Brd U ELISA result demonstrated the proliferation of CFs was increased in a dose-and time-dependent manner.Furthermore,the m RNA and protein level of SCAD were significantly decreased when subjected with 100 n M Ang II for 36 hours.Compared with control group,the m RNA and protein level of SCAD were seriously decreased in si RNA-1186 and Ang II groups,which was accordant with the enzyme activity of SCAD.Besides,ATP content was significantly lower in si RNA-1186 and Ang II groups.In addition,the expression of collagen I and collagen III were increased remarkably in si RNA-1186 and Ang II groups,which was consistent with the expression of a-SMA and the content of hydroxyproline.4.Compared with si RNA 1186 group,CFs pretreated with fenofibrate had an increased expression of SCAD and PPARα,increased enzyme activity of SCAD,increased the ATP content.Similarily,fenofibrate can increase expression of SCAD and PPARα,the enzyme activity of SCAD,the ATP content,ATP content in Ang II treated CFs.What’s more,fenofibrate attenuated Ang II or si RNA induced cardiac fibrosis.ConclusionIn summary,our study demonstrated that SCAD played an important role in cardiac fibrosis,which could be regulated by PPARα.These novel findings demonstrated that SCAD may be as a new target to prevent cardiac fibrosis.