Dillon Kolacz

Introduction. Physiologically-induced miRNA cardiac remodeling via exercise is the most beneficial medicine for heart disease. Smoking, obesity, diabetes, poor diet, hypertension, and inactivity all contribute to cardiovascular disease, which accounts for 1 in 2.9 deaths of Americans.⁷ The text focuses on three miRNAs, miRNA – 29, miRNA – 126, and miRNA – 143, that are upregulated/downregulated by exercise and their effects on heart tissue. These miRNAs are then juxtaposed against anabolic steroid use and high-fat diets to show how these factors also can affect cardiac remodeling. Methods. A review of studies involving animal subjects where blood and tissue samples were collected in experimental and control groups. Experimental groups were subjected to progressive overload cardiac training, and control groups were sedentary. RT-PCR utilized to measure levels of miRNA.^1,4 Results. miRNA – 29c levels increase in aerobic exercising subjects, while it is normally low in sedentary individuals.^1,6 This miRNA prevents collagen type I and II expression on the borders of myocardial infarction, which suggests that this miRNA is involved in antagonizing fibrotic deposition associated with heart disease. miRNA -126 also increases in aerobic exercising subjects. This miRNA modulates the effects of SPRED1 and PIK3R2 which negatively regulate the VEGF system.^1,3 By repressing SPRED1 and PIK3R2, VEGF signaling in endothelial cells is less negatively regulated. Although VEGF is secreted by cardiomyocytes in both pathological and physiological cardiac hypertrophy, it is less inhibited in physiological cardiac hypertrophy because of the upregulation of miRNA-126, which means more angiogenesis will occur with exercise.¹  miRNA – 143 levels were shown to be down-regulated in physiologically-induced cardiac hypertrophic subjects. miRNA-143 upregulates ACE2 in the heart. Because there is more miRNA-143 in sedentary individuals, ACE2 upregulation would cause more vascular tone – higher blood pressure.² This increase in total peripheral resistance, or afterload, could further induce cardiac remodeling – but pathologically. Similar pathologic remodeling can be induced from steroid use – as steroid use is associated with increased collagen/fibrotic deposition in cardiac tissue.⁸ The effects of anabolic steroid usage on cardiac tissue can be seen in both exercised and non-exercised groups. High-fat diets also promote cardiac remodeling – but negatively; therefore, diet alone can affect the structure and functionality of the heart.⁵ miRNA 29c is lower in subjects who are sedentary, which means that exercise may be a greater cardiovascular disease preventative mechanism than diet alone. Conclusion. Human experiments would be difficult due to multiple factors that are difficult to control, including diet, genetics, environmental factors, lifestyle choices, and life in general, including stressors and obligations. Further research on miRNA could potentially lead to highly-specific cardio-therapy without the need for exercise, but a challenge to this ideal scenario is that the current miRNA molecular/cellular mechanisms are unknown.^1,3,4

References

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