Sulfur dioxide ameliorates rat myocardial fibrosis by inhibiting endoplasmic reticulum stress.

Abstract

Myocardial remodeling occurs after myocardial infarction (MI), the leading cause of mortality worldwide. Although myocardial fibrosis plays an important role in the process of myocardial remodeling, there is not yet an effective method of reducing it. The aim of the present study was to determine the effects of sulfur dioxide (SO₂) on myocardial fibrosis and the possible mechanisms of these effects. SO₂ treatment reduced the extent of myocardial fibrosis and post-MI levels of collagens I and III in the left-ventricular myocardium. SO₂ also improved MI-induced thinning of the left ventricular wall while enlarging the left ventricular internal diameter. SO₂ was able to reduce matrix metalloproteinase (MMP)-9 activity and increase tissue matrix metalloproteinase inhibitor (TIMP)-1 content in myocardium after MI. However, the mechanism underlying these effects of SO₂ on myocardial fibrosis are unknown. Western blot analysis of endoplasmic reticulum (ER) stress-related proteins showed that glucose-regulated protein 78, C/EBP homologous protein, caspase-12, and phosphorylated eukaryotic initiation factor 2α expression levels were significantly increased in MI rats and decreased by SO₂ treatment. The ER stress promoter dithiothreitol reversed these effects of SO₂. In conclusion, SO₂ alleviated myocardial fibrosis in MI rats through a mechanism related to inhibition of excessive ER stress.