UPREGULATION OF PPET-1 AND DOWNREGULATION OF ENOS ASSOCIATE WITH VASCULAR REMODELING AND INFLAMMATION IN THE HEART AND KIDNEY OF RATS WITH HIGH FAT DIET

Abstract

Objective: Obesity alters several metabolic activities leading to cardiovascular diseases. The insulin resistance-caused obesity stimulates vasodilator and vasoconstrictor agent disturbances that ended up with cardiac vascular remodeling. This study aims to investigate the effect of obesity to the heart and kidney, focusing on inflammatory mediators associated with endothelial dysfunction. Design and method: Rats (3 months-old, weight 200 g) were divided into control (n = 6), and rats fed on high-fat diet (HFD) for 1 month (n = 6, OB1), 2 months (n = 6, OB2), and 4 months (n = 6, OB4). Then, rats were terminated, and the heart and kidney were harvested for histological quantification and the quantification of mRNA expression of inflammatory mediators, eNOS and ppET-1 using RT-PCR. Sirius Red staining was done to assess vascular remodeling and the immunohistochemistry staining of CD68 protein expression was performed to assess the localization of macrophage. Results: HFD induced high body weight compared to the control group. It was followed by increase of mRNA expression of NF-KB, MCP-1 and CD68 in heart of HFD groups compared to the control group, especially in OB4. Immunostaining revealed positive staining of macrophage (CD68) in the heart of OB groups. Histological staining of the kidney showed slight tubular injury and glomerulosclerosis in OB4 group. Long-term obesity promoted vascular remodeling with increased wall in the heart of OB4 group. OB4 group demonstrated upregulation of ppET-1 with downregulation of eNOS mRNA expression in the heart and kidney. Conclusions: HFD induced upregulation of ET-1 and downregulation of eNOS which may associate with cardiac vascular remodeling, kidney injury and inflammation in the heart and kidney.