Abstract 088: Exercise Training Restores miRNA-1 and -29c in Obese Preventing Pathological Cardiac Hypertrophy via Targets in the Collagen and Calcium- Signaling Pathway

Abstract

Introduction: Overweight and obesity are risk factors in several cardiovascular diseases that lead to the pathological cardiac hypertrophy (CH) phenotype. We previously reported that aerobic exercise training (AET) counteracts CH in obesity. Here, we evaluate the role of microRNAs (miRs) and target genes involved in the AET-induced prevention and improvement of ventricular compliance in CH of obese Zucker rats. Methods and Results: Zucker rats were assigned into four groups: 1) lean group (LZR), 2) obese (OZR), 3) trained lean group (LZR+TR) and 4) trained obese group (OZR+TR). The AET consisted of swimming training with 10 weeks duration sessions of 60 min, 1x/day, 5x/week with overload by 4% of body weight. Our results showed that there were no differences in the cardiomyocytes diameter, however; heart weight was higher in OZR (29% - 0,031 to 0,024mg/cm) compared to LZR group, due to increased cardiac intramuscular fat and collagen. AET prevented pathological CH in OZR+TR group normalizing heart weight. Cardiac miR-29c expression was reduced (47% - 43 to 100% of LZR) in OZR compared to LZR group paralleled by an increase of collagen fraction. AET restored miR-29c expression in OZR-TR along with the expression of its target gene collagen. In addition, miR-1 targets NCX1 gene. MiR-1 was upregulated (63% - 163 to 100%) while their target gene NCX1 was reduced (51% - 49 to 100%) in OZR compared to LZR group. Corroborate with NCX1, pPLB Ser16 was reduced in OZR group, indicating damage in calcium handling by obesity. Interestingly, AET normalized cardiac miR-1 and calcium signaling protein levels in OZR-TR group. Conclusion: Our findings show the AET as a non-pharmacological therapy for the prevention and even reversal of pathological CH and dysfunction in obesity. Together, the data suggests that miR-1 and -29c play key role in cardiac remodeling which could be used as potential therapeutic target for cardiac disorders.