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 MI^2,6. 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 disease^3,4. 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 CVD^1,2,4,6,9,10.

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2. Lin, Ruby C.Y., Weeks, Kate L., et al. PI3K(p110α) Protects Against Myocardial Infarction-Induced Heart Failure. Arteriosclerosis, Thrombosis, and Vascular Biology. 2010;30:724-732/ doi: 10.1161/ATVBAHA.109.201988.
3. Lovic D, Narayan P, Pittaras A, Faselis C, Doumas M, Kokkinos P. Left ventricular hypertrophy in athletes and hypertensive patients. J Clin Hypertens. 2017;00:1–5.
4. Masi L, N, Serdan T, D, A, Levada-Pires A, C, Hatanaka E, Silveira L, R, Cury-Boaventura M, F, Pithon-Curi T, C, Curi R, Gorjão R, Hirabara S, M, Regulation of Gene Expression by Exercise-Related Micrornas. Cell Physiol Biochem 2016;39:2381-2397
5. Mazidi M., Penson, P. Relationship between long noncoding RNAs and physiological risk factors of cardiovascular disease. J Clin Lipidol. S1933-2874(17)30079-X. doi: 10.1016/j.jacl.2017.03.009.
6. Melo SFS, Barauna VG, Neves VJ, et al. Exercise training restores the cardiac microRNA-1 and −214 levels regulating Ca²⁺handling after myocardial infarction. BMC Cardiovascular Disorders. 2015;15:166. doi:10.1186/s12872-015-0156-4.
7. Naga Prasad SV, Gupta MK, Duan Z-H, et al. A unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks. Gupta S, ed. PLoS ONE. 2017;12(3):e0170456. doi:10.1371/journal.pone.0170456.
8. Preventing the Top Killer – Heart Disease. Nebraska Medicine. https://www.nebraskamed.com/heart/preventing-the-top-killer–heart-disease. Published March 10, 2017. Accessed June 4, 2017.
9. Samanta S, Balasubramanian S, Rajasingh S, Patel U, Dhanasekaran A, Dawn B, Rajasingh J. MicroRNA: A new therapeutic strategy for cardiovascular diseases. Trends Cardiovasc Med. 2016 Jul;26(5):407-19. doi: 10.1016/j.tcm.2016.02.004.
10. Xu J, Liu Y, Xie Y, Zhao C, Wang H. Bioinformatics Analysis Reveals MicroRNAs Regulating Biological Pathways in Exercise-Induced Cardiac Physiological Hypertrophy. BioMed Research International. 2017;2017:2850659. doi:10.1155/2017/2850659.