title: Hypercholesterolemia Up-Regulates the Expression of Intermedin and Its Receptor Components in the Aorta of Rats via Inducing the Oxidative Stress.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Di
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jiayue
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Changhai Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Su
authors.affiliation: Laboratory of Endocrine and Metabolic Diseases, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Sen
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Endocrine and Metabolic Diseases, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xiangxun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China chenxp13@aliyun.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
mesh_terms: D053607:Adrenomedullin / Q000097:blood / Q000235:genetics*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D058286:Calcitonin Receptor-Like Protein / Q000378:metabolism; D006937:Hypercholesterolemia / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D009479:Neuropeptides / Q000097:blood / Q000235:genetics*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D058262:Receptor Activity-Modifying Protein 1 / Q000378:metabolism; D058263:Receptor Activity-Modifying Protein 2 / Q000378:metabolism; D058264:Receptor Activity-Modifying Protein 3 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C499411:Adm2 protein, rat; D000975:Antioxidants; D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; D008074:Lipoproteins; D009479:Neuropeptides; D016877:Oxidants; D012333:RNA, Messenger; C545508:Ramp1 protein, rat; C545509:Ramp2 protein, rat; C545510:Ramp3 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D011956:Receptors, Cell Surface; D053607:Adrenomedullin
keywords: Hypercholesterolemia; Intermedin; Oxidative stress