Retinol exerts therapeutic effect on myocardial infarction through regulation of immune inflammatory cells and Cx43 expression

Abstract

Purpose: To investigate the effect of retinol on cardiac fibroblast proliferation in vitro and on fibrosis formation in mice in vivo. Methods: Proliferative potential of fibroblasts was determined using cell counting kit-8 assay. Acute myocardial infarction (AMI) was induced in mice via ligation of the left side coronary artery. In myocardial tissues, concentration of TNF-α was determined using enzyme-linked immunosorbent assay (ELISA) assay. Results: Exposure to retinol significantly suppressed cardiac fibroblast proliferation under ischemia, when compared to untreated fibroblasts (p < 0.05). However, exposure of cardiac fibroblasts to retinol did not produce toxicity at a dose of 10 μM under normal conditions. In contrast, exposure to normal levels of oxygen, glutamine and glucose significantly reversed the inhibitory potential of retinol against fibroblasts during ischemia (p < 0.05). Treatment of mice with retinol at a dose of 5 mg/kg reversed the AMI-mediated increase in hydroxyproline level in myocardial tissues. Retinol treatment of AMI mice caused significant elevation in the number of CD31+ capillaries in myocardial tissues. Increase in TNF-α by AMI in cardiac tissues of mice was reversed by treatment with retinol at a dose of 5 mg/kg. The retinol treatment also caused significant reversal of AMI-induced down-regulation of Cx43 protein (p < 0.05). Conclusion: Retinol enhanced the proliferation of fibroblasts under ischemic conditions and prevented fibrosis in mice with AMI. Moreover, retinol targeted TNF-α production and upregulated Cx43 expression in myocardial tissues of mice with AMI. Thus, retinol may be useful for the management of myocardial infarction.