·To establish a novel mice model of heart failure with preserved ejection fraction (HFpEF).

·Sixteen 8-week-old SPF grade male and female C57BL/6J mice each were randomly divided into control group or model group (n=8 per group). The model group was given high-fat diet containing 60% fat and drinking water containing 0.5 g/L N^ω-nitro-L-arginine methyl ester hydrochloride (L-NAME). The control group was given routine feed and drinking water. The ratio of peak early mitral velocity to peak late mitral velocity (E/A ratio) and the ratio of peak early mitral velocity to peak early diastolic mitral annular velocity (E/E' ratio) were detected by echocardiography every two weeks to evaluate left ventricular diastolic function. At the 16th week after modeling, the myocardial hypertrophy and fibrosis were examined by Masson staining and hematoxylin-eosin staining. The levels of serum triacylglycerol (TAG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-Ch) and low-density lipoprotein cholesterol (LDL-Ch) were detected by automatic biochemical analyzer.

·HFpEF appeared in the male mice at 8 weeks after high-fat diet and L-NAME administration, with a significant increase in E/A ratio and E/E′ ratio in comparison to the male control group (both P=0.000). There was no significant difference in the left ventricular ejection fraction (LVEF) between male model group and male control group. On the other hand, the female mice fed with high-fat diet and drinking water containing L-NAME also displayed obvious HFpEF after 8 weeks. E/A ratio and E/E' ratio in female model group were significantly higher than those in the female control group (P=0.000, P=0.001). There was no significant difference in LVEF between female model group and female control group. At the 16th week after modeling, both male and female mice still displayed the characteristics of HFpEF. Systolic blood pressure and diastolic blood pressure of male and female model group were significantly higher than those of respective control groups. Male or female mice with HFpEF showed obvious myocardial hypertrophy and fibrosis along with left ventricular remodeling. The serum levels of TAG, TC, HDL-Ch and LDL-Ch in the model groups were significantly higher than those in the respective control groups.

·High-fat feeding combined with L-NAME administration can induce HFpEF in both male and female mice.