Meng Qingtao, Shi Di, Feng Jiayue, Su Yanling, Long Yang, He Sen, Wang Si, Wang Yong, Zhang Xiangxun, Chen Xiaoping
Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
Department of Cardiology, Changhai Hospital, the Second Military Medical University, Shanghai, China.
Ann Clin Lab Sci. 2016 Winter;46(1):5-17.
Hypercholesterolemia can cause damage to the artery. Intermedin (IMD) is a novel member of the calcitonin gene-related peptide family. This study aims to investigate the aortic expression of IMD and its receptors in hypercholesterolemia without atherosclerosis.
Male Wistar rats were fed with high cholesterol diet, with or without simvastatin and vitamin C. 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 was determined, and the corresponding protein level of the CRLR/RAMPs was also assessed.
The hypercholesterolemia rats without atherosclerotic lesion manifested a higher level of MDA and SOD and the plasma IMD elevated. Increased expression of IMD and all its receptor components (CRLR, RAMP1, RAMP2, and RAMP3) were displayed within the aorta. 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.
The up-regulated expression of IMD is observed within the aorta of the hypercholesterolemia rats. In addition, the oxidative stress participates in the up-regulation.
高胆固醇血症可导致动脉损伤。中间介质（IMD）是降钙素基因相关肽家族的新成员。本研究旨在探讨无动脉粥样硬化的高胆固醇血症大鼠主动脉中IMD及其受体的表达情况。
雄性Wistar大鼠喂食高胆固醇饮食，同时给予或不给予辛伐他汀和维生素C。测定血浆和主动脉中的丙二醛（MDA）和超氧化物歧化酶（SOD）作为氧化应激生物标志物。采用放射免疫分析法评估血浆IMD。在主动脉内，测定IMD及其受体成分的mRNA表达，并评估CRLR/RAMPs的相应蛋白水平。
无动脉粥样硬化病变的高胆固醇血症大鼠表现出较高水平的MDA和SOD，血浆IMD升高。主动脉内IMD及其所有受体成分（CRLR、RAMP1、RAMP2和RAMP3）的表达均增加。辛伐他汀通过改善血脂间接减轻氧化应激，而维生素C直接降低氧化应激而不干扰血脂。辛伐他汀和维生素C均改善了主动脉损伤，降低了血浆IMD水平，并恢复了主动脉内IMD及其受体的表达。
在高胆固醇血症大鼠的主动脉中观察到IMD表达上调。此外，氧化应激参与了这种上调过程。
