Cyclosporine Treatment Increases The ACE/ACE2 Ratio in Adipose Tissue and Aorta

Abstract

Objective: The renin-angiotensin system (RAS) mainly functions in the regulation of vascular tone. Since the perfusion and storage capacity of adipose tissue is largely dependent on vessel density and tone, factors that modulate vasoactive RAS components may affect adipose tissue metabolism. Cyclosporine, an immunosuppressive drug, has some detrimental effects on the vascular system and kidneys by modulating the components of the RAS. However, the effect of cyclosporine on adipose tissue is still not clear. In this study, the impact of cyclosporine on mRNA expressions of some "RAS components" in the aorta and epididymal adipose tissue of rats were investigated. Materials and Methods: Rats were injected subcutaneously with cyclosporine at a dose of 25 milligrams per kilogram per day for 1 week. Angiotensin II, angiotensin (1-7), blood urea nitrogen and creatinine levels were examined in serum samples of rats. mRNA expressions of RAS components in the aorta and epididymal adipose tissue, and hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) in epididymal adipose tissue were determined. In addition, histopathological examinations of the adipose tissue were performed. Results: Cyclosporine administration significantly suppressed the expression of angiotensin-converting enzyme 2 (ACE2) in both the aorta and adipose tissue. Accordingly, it caused a significant increase in the ACE/ACE2 ratio. However, it did not affect the adipose tissue HIF-1 and VEGF expressions. When examined histopathologically, no change was observed in the vascular density of adipose tissue due to cyclosporine. Conclusion: It was thought that the increase in the ACE/ACE2 ratio might be an adaptation that protects the adipose tissue against the systemic effect of cyclosporine.

Keywords

• Cyclosporine
• adipose tissue
• angiotensin-converting enzyme 2
• vascular density

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