Exercise Induced Changes on miRNA Expression and Its Effect on Cardiovascular Disease

Brittney Jackson

Introduction: Cardiovascular diseases (CVD) are the leading cause of death in the United States and consume a significant amount of healthcare expenditures8. It is well researched and known that gene expression patterns are substantially altered in cardiac hypertrophy, myocardial infarction (MI), and heart failure5. microRNAs (miRNAs) are short non-coding RNAs that can target multiple molecules to regulate proteins and are essential for normal development and physiology of the heart. Dysregulation of these miRNAs is linked to CVD and serve as biomarkers1. Methods: Mice were placed under vigorous physical aerobic exercise including swimming and running 5 days per week for 8-10 weeks following an induced MI2,6. miRNA levels were measured and evaluated in regard to increased or decreased expression and their effect on cardiovascular health. This was accomplished by taking left ventricle samples and homogenizing them in TRIZOL. RNA was isolated and specific miRNAs were analyzed using PCR6. Echocardiograms and oxygen stats were used to measure and evaluate the function of the heart before and following the exercise program6. Results: The physiological exercise-induced cardiac hypertrophy leads to an increase cardiac PI3K activity whereas pathological hypertrophy decreases PI3K activity and causes heart failure. Using microarray analysis, it was determined that PI3K-regulated miRNA was correlated with cardiac function2. Increased PI3K activity improved the lifespan or the cardiac function in those exposed to PI3K with a preexisting cardiomyopathy2. Studies show post MI there are impaired intracellular Ca2+ handling due to altered expression and function of the sodium/calcium exchanger (NCX), Serca-2a, and phospholamban (PLP) in cardiomyocytes while these proteins are restored by exercise6. In humans, positive outcomes of exercise post-MI include: favorable left ventricular remodeling, and improvement of left ventricular functional capacity, ejection fraction, and early diastolic filing10. In animal models, exercise produces benefits such as reduction of total collagen content and returned intracellular Ca2+ handling, sensitivity, and contractile function in isolated cardiomyocytes6. Conclusions: miRNAs can be useful for the development and targeting of treatment plans1. Following exercise, specific miRNAs are expressed and/or repressed which can further prevent the progression of cardiovascular disease3,4. Exercise has been proven to treat, prevent, and improve CVD7. Research has shown the important role miRNAs play in regulating CVD and how they are upregulated or down regulated in response to exercise9. Multiple studies confirm the need for more research in creating exercise plans and regiments to treat various CVD1,2,4,6,9,10.

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