Exercise Regulates MicroRNAs to Preserve Coronary and Cardiac Function in the Diabetic Heart
| Autor: | Melanie Wei, Meihua Jin, Jason Kar Sheng Lew, Eugene Saw, Mikiyasu Shirai, Dong Yun Zhan, Cheng-Kun Du, Keiji Umetani, James T. Pearson, Rajesh Katare, Daryl O. Schwenke, Nilanjan Ghosh, Hirotsugu Tsuchimochi |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cardiac function curve medicine.medical_specialty Time Factors Heart disease Diabetic Cardiomyopathies Physiology Disease 030204 cardiovascular system & hematology Ventricular Function Left Article Running Mice 03 medical and health sciences 0302 clinical medicine Physical Conditioning Animal Internal medicine Diabetes mellitus microRNA medicine Animals Cardioprotection Ventricular Remodeling medicine.diagnostic_test business.industry Myocardium Type 2 Diabetes Mellitus medicine.disease Fibrosis Exercise Therapy Disease Models Animal MicroRNAs 030104 developmental biology Diabetes Mellitus Type 2 Gene Expression Regulation Angiography Cardiology Female Cardiology and Cardiovascular Medicine business Signal Transduction |
| Zdroj: | Circ Res |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.120.317604 |
| Popis: | Rationale: Diabetic heart disease (DHD) is a debilitating manifestation of type 2 diabetes mellitus. Exercise has been proposed as a potential therapy for DHD, although the effectiveness of exercise in preventing or reversing the progression of DHD remains controversial. Cardiac function is critically dependent on the preservation of coronary vascular function. Objective: We aimed to elucidate the effectiveness and mechanisms by which exercise facilitates coronary and cardiac-protection during the onset and progression of DHD. Methods and Results: Diabetic db/db and nondiabetic mice, with or without underlying cardiac dysfunction (16 and 8 weeks old, respectively) were subjected to either moderate-intensity exercise or high-intensity exercise for 8 weeks. Subsequently, synchrotron microangiography, immunohistochemistry, Western blot, and real-time polymerase chain reaction were used to assess time-dependent changes in cardiac and coronary structure and function associated with diabetes mellitus and exercise and determine whether these changes reflect the observed changes in cardiac-enriched and vascular-enriched microRNAs (miRNAs). We show that, if exercise is initiated from 8 weeks of age, both moderate-intensity exercise and high-intensity exercise prevented the onset of coronary and cardiac dysfunction, apoptosis, fibrosis, microvascular rarefaction, and disruption of miRNA signaling, as seen in the nonexercised diabetic mice. Conversely, the cardiovascular benefits of moderate-intensity exercise were absent if the exercise was initiated after the diabetic mice had already established cardiac dysfunction (ie, from 16 weeks of age). The experimental silencing or upregulation of miRNA-126 activity suggests the mechanism underpinning the cardiovascular benefits of exercise were mediated, at least in part, through tissue-specific miRNAs. Conclusions: Our findings provide the first experimental evidence for the critical importance of early exercise intervention in ameliorating the onset and progression of DHD. Our results also suggest that the beneficial effects of exercise are mediated through the normalization of cardiovascular-enriched miRNAs, which are dysregulated in DHD. |
| Databáze: | OpenAIRE |
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