Effects of vitexin on cardiac hypertrophy and fibrosis after myocardial infarction in rats through modulation of the exchange proteins activated directly by cyclic adenosinemonophosphate 1/calcium/calmodulin-dependent protein kinase Ⅱ pathway
Objective To explore the role of vitexin in regulating the exchange proteins activated directly by cyclic adenosinemonophosphate1(Epac1)/calcium/calmodulin-dependent protein kinaseⅡ(CaMKⅡ)signaling pathway and inhibiting myocardial cell hypertrophy and fibrosis in rats after myocardial infarction(MI).Methods Twenty-four SD rats were randomly divided into sham surgery group,MI group,and vitexin group.The MI model was established by left anterior descending coronary artery ligation.In the sham surgery group,the left anterior descending coronary artery was only threaded without ligation.Changes in rat cardiac function were assessed.Cardiac pathological changes were observed using hematoxylin-eosin(HE)staining,and fibrosis was assessed using Sirius Red staining.Mitochondrial damages in cardiocytes were examined by electron microscopy.Western blot was used to detect protein changes,including Epac1 and CaMKⅡ.Results(1)Four weeks after MI,compared with the sham surgery group,left ventricular fractional shortening(LVFS)and left ventricular ejection fraction(LVEF)in the MI group decreased(P<0.01),and left ventricular internal diameter at end-systolic(LVIDs),left ventricular internal diameter at end-diastolic(LVIDd),left ventricular posterior wall thickness at end-diastolic(LVPWd),and left ventricular posterior wall thickness at end-systolic(LVPWs)inceased(P<0.01).The vitexin group showed significant decreases in LVIDs,LVIDd,LVPWs,and LVPWd and increases in LVFS and LVEF compared to the MI group(P<0.05).(2)Vitexin reduced the heart weight index(P<0.01)and decreased the cross-sectional area of myocardial cells in rats of MI group,while alleviating myocardial fibrosis in the left ventricular wall(P<0.01).In the vitexin group,myocardial cytoplasmic mitochondrial swelling was reduced,mitochondrial morphology was more intact,and vacuole formation was decreased compared to the MI group.(3)Western blot results showed that vitexin inhibited Epac1 activation(P<0.01),suppressed the activation of downstream CaMKⅡ and the phosphorylation of extracellular regulated kinase(ERK)(P<0.01),simultaneously inhibited upregulation of B-cell lymphoma-2(Bcl-2)-associated X protein(Bax)(P<0.05),upregulated Bcl-2(P<0.01),and inhibited the activation of apoptotic protein Cleaved-Caspase 3(P<0.05).Conclusion Vitexin may improve cardiac function,inhibit myocardial hypertrophy,and reduce fibrosis after MI by suppressing the Epac1/CaMKⅡ pathway.
VitexinMyocardial ischemiaApoptosisExchange proteins activated directly by cyclic adenosinemonophosphate 1Calcium/calmodulin dependent protein kinase Ⅱ
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