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Diabetic cardiomyopathy (DCM) is a form of idiopathic heart disease, with signs including hypertrophy of myocardial cells, hypertension-independent fibrosis and coronary artery disease. Considering the involvement of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in diabetes, it was hypothesized that DDAH2 may be beneficial to cardiac function and myocardial fibrosis during the progression of DCM with involvement of the DDAH/asymmetric NG, NGdimethyl-L-arginine (ADMA)/nitric oxide synthase (NOS)/nitric oxide (NO) signaling pathway. Following establishment of diabetic rat models, diabetes-related blood biochemical indices and cardiac function were measured in diabetic rats treated with lentivirus expressing DDAH2, short hairpin RNA against DDAH2, or L-NNA (inhibitor of NOS) to identify the roles of DDAH2 in DCM. The functional roles of DDAH2 in DCM were further determined through detection of the levels of collagen I, matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2). The H9C2 myocardial cell line was selected for in vitro experiments. The effects of DDAH2 on the migration of myocardial cells under high glucose conditions were also examined. To further investigate the underlying regulatory mechanism of DDAH2 in DCM, the contents of ADMA and NO, and the activities of DDAH and NOS were observed. The DCM model rats treated with DDAH2 exhibited reduced left ventricular end-diastolic pressure, and decreased blood glucose, total cholesterol, triglyceride, fasting blood glucose, and fasting insulin levels, but exhibited increased left ventricular systolic pressure and maximum rate of left ventricular pressure rise/fall levels in myocardial tissues. Myocardial cells under high glucose conditions treated with DDAH2 showed reductions in collagen I, MMP2 and TIMP2, indicating that DDAH2 reduced cell migration. Decreased levels of ADMA and NO but increased levels of DDAH and NOS were observed following treatment with DDAH2, indicating that the DDAH/ADMA/NOS/NO pathway was activated. These results reveal that the overexpression of DDAH2 attenuates myocardial fibrosis and protects against DCM through activation of the DDAH/ADMA/NOS/NO pathway in DCM rats. These results indicate that DDAH2 is a potential therapeutic candidate for the treatment of DCM.

ObjectiveClinical trials have recently shown a connection between nonalcoholic fatty liver disease (NAFLD) and empagliflozin. This paper aimed at comprehensively assessing the effectiveness and security of empagliflozin in NAFLD patients.MethodsPubMed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wan-Fang digital database, VIP, and WHO ICTRP were searched for randomized controlled trials (RCTs) on the role of empagliflozin in NAFLD from inception to November 2, 2021. For continuous dating, we used values of mean differences (MD) to present.ResultsA total of four articles involving 244 NAFLD patients were included. Compared with the control group, empagliflozin could significantly reduce the body mass index (BMI) (MD: −0.98 [95% CI: −1.87, −0.10], p = 0.03), liver stiffness measurement (LSM) (MD: 0.49 [95% CI: −0.93, −0.06], p = 0.03), aspartate aminotransferase (AST) (MD: −3.10 [95% CI: −6.18, −0.02], p = 0.05), homeostasis model assessment of insulin resistance (HOMA-IR) (MD: −0.45 [95% CI: −0.90, 0.00], p = 0.05) of the treatment group.ConclusionsEmpagliflozin can improve body composition, insulin resistance, and liver fibrosis and decrease the hepatic enzymes in patients with NAFLD. Empagliflozin emerges as a new option for treating patients with NAFLD. However, further research shall determine the efficacy and safety of empagliflozin in NAFLD.

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