Cardioprotective effect of nicorandil on isoproterenol induced cardiomyopathy in the Mdx mouse model
| Autor: | Margaret Haberman, Michael W. Lawlor, Jennifer L. Strande, Ngoc Thien Lam, Rachel T. Sullivan, Muhammad Afzal, Margaret Beatka |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cardiac function curve
Duchenne muscular dystrophy Xanthine Oxidase mdx mouse Cardiac fibrosis Cardiomyopathy 030204 cardiovascular system & hematology Pharmacology medicine.disease_cause Ventricular Function Left 03 medical and health sciences 0302 clinical medicine DMD medicine Animals Diseases of the circulatory (Cardiovascular) system Myocytes Cardiac Nicorandil NADPH oxidase biology Superoxide Dismutase business.industry Research Isoproterenol NADPH Oxidases Stroke Volume medicine.disease Fibrosis Muscular Dystrophy Duchenne Disease Models Animal RC666-701 Mice Inbred mdx biology.protein cardiovascular system Female Cardiomyopathies Reactive Oxygen Species Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | BMC Cardiovascular Disorders BMC Cardiovascular Disorders, Vol 21, Iss 1, Pp 1-12 (2021) |
| ISSN: | 1471-2261 |
| Popis: | Background Duchenne muscular dystrophy (DMD) associated cardiomyopathy is a major cause of morbidity and mortality. In an in vitro DMD cardiomyocyte model, nicorandil reversed stress-induced cell injury through multiple pathways implicated in DMD. We aimed to test the efficacy of nicorandil on the progression of cardiomyopathy in mdx mice following a 10-day treatment protocol. Methods A subset of mdx mice was subjected to low-dose isoproterenol injections over 5 days to induce a cardiac phenotype and treated with vehicle or nicorandil for 10 days. Baseline and day 10 echocardiograms were obtained to assess cardiac function. At 10 days, cardiac tissue was harvested for further analysis, which included histologic analysis and assessment of oxidative stress. Paired student’s t test was used for in group comparison, and ANOVA was used for multiple group comparisons. Results Compared to vehicle treated mice, isoproterenol decreased ejection fraction and fractional shortening on echocardiogram. Nicorandil prevented isoproterenol induced cardiac dysfunction. Isoproterenol increased cardiac fibrosis, which nicorandil prevented. Isoproterenol increased gene expression of NADPH oxidase, which decreased to baseline with nicorandil treatment. Superoxide dismutase 2 protein expression increased in those treated with nicorandil, and xanthine oxidase activity decreased in mice treated with nicorandil during isoproterenol stress compared to all other groups. Conclusions In conclusion, nicorandil is cardioprotective in mdx mice and warrants continued investigation as a therapy for DMD associated cardiomyopathy. |
| Databáze: | OpenAIRE |
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