Objective:To explore the relationship between telomere attrition and heart failure with preserved ejection fraction(HFpEF).Methods:Wild-type C57BL/6J mice,second-generation mTRKO mice(mTRG2)and third-generation mTRKO mice(mTRG3)were divided into control and HFpEF groups by a random sampling method(n=8 in each group).The control group was given routine feed and normal drinking water,while the model group was given 60％high-fat diet and drinking water containing 0.5 g/L N-nitro-L-arginine methyl ester(L-NAME)for 16 weeks.Left ventricular ejection fraction(LVEF),peak early to late trans-mitral flow velocity ratio(E/A),peak early diastolic mitral valve flow to annular motion velocity ratio(E/e'),global longitudinal strain(GLS),left ventricular anterior(LVAWd)and posterior wall dimensions(LVPWd)were assessed every 2 weeks.Systolic(SBP)and diastolic blood pressure(DBP)and lipid profile were determined at 16 weeks.Results:After 16 weeks of treatment with high-fat diet and L-NAME drinking water,there were no significant differences in LVEF values between groups in each genotype.Wild-type mice showed a decrease in diastolic function indices including a increse in E/e',E/A,LVAWd and LVPWd and a decrease in GLS at 8 weeks.HFpEF phenotype was observed in mTRG2 at 6 weeks and in mTRG3 at 4 weeks,respectively.After 16 weeks of modeling,lipid levels,SBP and DBP were significantly higher in the HFpEF group compared to control group of same genotypes(P＜0.05).Conclusion:Telomere attrition accelerates the development of HFpEF with the combination of high-fat diet and L-NAME drinking water.
Heart failure with preserved ejection fractionTelomere attritionGene knock-out
维普
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