PP.13.15

Abstract

Objective: Hypercholesterolemia can cause damage to the artery before the atherosclerotic lesion has formed. Intermedin (IMD) is a novel member of the calcitonin gene-related peptide family. Endogenous IMD is reported to participate in several cardiovascular pathological states. Using the rats fed with high-cholesterol diet, this study aims to investigate the aortic expression of IMD and its receptors in hypercholesterolemia without atherosclerosis. Furthermore, by the antioxidant intervention, we also explore the influence of oxidative stress. Design and method: Male Wistar rats were fed with high cholesterol diet, with or without concurrent administration of simvastatin and vitamin C. The serum lipid levels were measured, and the aortic histopathology features were examined. Both the malondialdehyde (MDA) and superoxide dismutase (SOD) in plasma and aorta were determined as the oxidative stress biomarkers. The plasma IMD was assessed by radioimmunoassay. Within the aorta, the mRNA expression of IMD along with its receptor components were determined by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and the corresponding protein level of the CRLR/RAMPs were assessed by Western blot analysis. Results: The hypercholesterolemia rats without atherosclerotic lesion manifested higher level of MDA and SOD. The IMD in plasma was elevated. Within the aorta, increased expression of IMD and all its receptor components (CRLR, RAMP1, RAMP2, and RAMP3) were displayed. The simvastatin indirectly attenuated oxidative stress by improving lipid profiles, while the vitamin C directly reduced oxidative stress without interfering with the serum lipids. Both simvastatin and vitamin C ameliorated the aortic injury, decreased the plasma IMD level, and recovered the expression of IMD and its receptors within the aorta. Conclusions: For the first time, the up-regulated expression of IMD is observed within the aorta of the hypercholesterolemia rats, demonstrating the pathophysiological role which IMD has performed in hypercholesterolemia absent of atherosclerosis lesion. In addition, the oxidative stress is evidenced to participate in the up-regulation.