Abstract 12790: Impaired Extracellular Matrix Turnover is Ameliorated by Exercise Training in Short-Term Experimental Diabetic Cardiomyopathy
The importance of exercise training (ExT) in treatment of diabetic cardiomyopathy has been reported in recent studies; however, only limited data can be found regarding the effects of exercise training on early stages of left ventricle (LV) remodeling in diabetes mellitus (DM). We hypothesized that ExT could attenuate the early LV remodeling induced by experimental DM. Male Wistar rats were divided in 4 groups: sedentary control (SC, n=9), trained control (TC, n=13), sedentary diabetic (SD, n=20) and trained diabetic (TD, n=17). Diabetes was induced by streptozotocin (45 mg/kg, i.v.). Training program was initiated at the onset of DM and consisted of 4 weeks running on a treadmill (13 m/min, 60 min/day, 5 days/week). Deaths were registered during the 4-week period. At the end of the experiments, hearts were collected (n=8-10/group) for histological analysis of LV morphology (hematoxylin-eosin staining) and collagen content (picrosirius red staining). Also, fresh LV fragments were isolated for gene expression analysis of the following interstitial proteins: collagens types I and III, metalloproteinases (MMPs) 2 and 9, and transforming growth factor (TGF)-1. We verified high mortality in SD animals (60% vs. 0% in SC, p<0.05), whereas it was attenuated in TD group (23.5%, p>0.05 vs. SC). SD group also showed an increase in both cross-sectional area (mean±SEM) of myocytes (SD: 227.65 ± 3.10um2 and SC: 213.06 ± 2.69um2, p<0.05) and collagen content (SD: 6.27 ± 0.23% and SC: 5.53 ± 0.15%, p<0.05). TD group exhibited reduction in myocyte cross-sectional area (143.49 ± 3.19um2, p<0.05 vs. SC), but with respect to collagen content it was similar to SC animals (6.03 ± 0.23%, p>0.05). Analysis of gene expression revealed downregulation of collagen I (2.9-fold) and III (6.7-fold), as well as lower expression of MMP-2 (2.3-fold) in SD (p<0.05 vs. SC). TD group showed decreased levels of mRNA for MMP-9 (5.8-fold) and unchanged gene expression of MMP-2 when compared to SC (p>0.05). MMP-2 (2.8-fold) and TGF-1 (4.5-fold) were upregulated only in TC group (p<0.05 vs. SC). These results indicate that ExT enhances the balance between extracellular matrix synthesis and degradation, thus playing a role against specific mechanisms responsible for LV fibrosis observed in diabetes.
Author Disclosures: F.S. Silva: None. D.N. Araújo: None. R.H. Bortolin: None. J.M. Silva: None. A.A. Rezende: None. B.A. Abreu: None. F.A. Dias: None.
- © 2014 by American Heart Association, Inc.