Abstract 311: Cardiac Hypertrophy and Epicardial Fat Inflammation in Vitamin D-Deficient and Hypercholesterolemic Swine

Abstract

Introduction: Vitamin D is a sectosteroid that functions through Vitamin D receptor (VDR), a transcription factor, which controls the transcription of many targets genes. Vitamin D deficiency has been linked with cardiovascular diseases, including heart failure and coronary artery disease. Suppressor of cytokine signaling (SOCS)-3 regulates different biological processes such as inflammation and cellular differentiation and is an endogenous negative regulator of cardiac hypertrophy. Objective: The purpose of this study was to test the hypothesis that vitamin D deficiency causes decreased expression of VDR and SOCS-3 in cardiomyocytes, and this correlates with cardiac hypertrophy and increased pro-inflammatory profile in epicardial adipose tissue. Methods: Eight female Yucatan miniswine were fed vitamin D-sufficient (900 IU/d) or vitamin D-deficient hypercholesterolemic diet. Complete lipid profile, comprehensive metabolic panel, and serum 25(OH)D levels were regularly measured. After 12 months animals were euthanized and histological and immunohistochemical studies were performed on myocardium and epicardial fat. The mRNA transcripts of VDR and SOCS-3 in the myocardium and epicardial fat tissue were quantified by qPCR. Results: Histological studies showed cardiac hypertrophy, as judged by cardiac myocyte cross sectional area, in vitamin D-deficient group. Immunohistochemical and real-time PCR analyses showed significantly decreased protein and mRNA expression of VDR and SOCS-3 in cardiomyocytes of vitamin D-deficient animals. Epicardial adipose tissue from vitamin D-deficient group had significantly higher expression of TNF-α, IL-6, MCP-1, and adiponectin in association with increased inflammatory cellular infiltrate. Interestingly, epicardial fat from vitamin D-deficient group had significantly decreased expression of SOCS-3. Conclusion: These data suggest that vitamin D deficiency induces hypertrophy in cardiomyocytes which is associated with decreased expression of VDR and SOCS-3. Vitamin D deficiency is also associated with increased inflammatory markers in epicardial fat. Activity of VDR in the body is controlled through regulation of vitamin D metabolites. Therefore, restoration of VDR function by supplementation of VDR ligands in vitamin D- deficient population might be helpful in reducing inflammation and cardiovascular risk.