Urocortin 2 Gene Transfer Reduces the Adverse Effects of a Western Diet on Cardiac Function in Mice
| Autor: | Young Chul Kim, N. Chin Lai, Tracy Guo, Bing Xia, Zhenxing Fu, Mei Hua Gao, Dimosthenis Giamouridis, H. Kirk Hammond |
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| Rok vydání: | 2019 |
| Předmět: |
Cardiac function curve
medicine.medical_specialty Corticotropin-Releasing Hormone viruses Mice Transgenic Type 2 diabetes medicine.disease_cause Ventricular Function Left Mice 03 medical and health sciences 0302 clinical medicine Insulin resistance Transduction Genetic Internal medicine Diabetes mellitus Genetics medicine Animals Homeostasis Adverse effect Molecular Biology Adeno-associated virus Urocortins 030304 developmental biology Heart Failure Urocortin 0303 health sciences business.industry Myocardium Gene Transfer Techniques Original Articles Dependovirus medicine.disease Glucose Endocrinology Diet Western Echocardiography 030220 oncology & carcinogenesis Heart failure Molecular Medicine business Signal Transduction |
| Zdroj: | Hum Gene Ther |
| ISSN: | 1557-7422 1043-0342 |
| Popis: | Diabetes mellitus is associated with increased risk of heart failure. It has been previously demonstrated in mice that a single injection of adeno-associated virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal in models of insulin resistance and improves the function of the failing heart. The present study tested the hypothesis that UCn2 gene transfer would reduce diabetes-related left ventricular (LV) dysfunction. Eight-week-old C57BL6 male mice were fed a Western diet (WD; 45% fat, 35% carbohydrate) for 40 weeks. At week 30, they received saline or AAV8.UCn2 (2 × 10(13) genome copies/kg) via intravenous injection. Ten weeks after gene transfer, fasting blood glucose, glucose tolerance, and cardiac function were measured via echocardiography and in vivo measurement of LV contractile function, and the results were compared to those of mice fed normal chow (NC; 10% fat; 70% carbohydrate). The contents of key LV signaling proteins were also measured to probe mechanisms. WD increased 12 h fasting glucose (WD: 190 ± 11 mg/dL, n = 8; NC: 105 ± 12 mg/dL, n = 7; p = 0.0004). WD tended to reduce LV peak +dP/dt (p = 0.08) and LV peak –dP/dt (p = 0.05). LV ejection fraction was unchanged. Among WD-fed mice, UCn2 gene transfer reduced 12 h fasting glucose (WD-UCn2: 149 ± 6 mg/dL, n = 8; WD-Saline: 190 ± 11 mg/dL, n = 8; p = 0.012), increased LV peak +dP/dt (p |
| Databáze: | OpenAIRE |
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