title: Increased expression of calcium-sensing receptors in atherosclerosis confers hypersensitivity to acute myocardial infarction in rats.
abstract: Acute myocardial infarction (AMI) is a leading cause of death worldwide. Most cases of AMI result from coronary atherosclerosis (AS). The pathogenic mechanisms underlying AS lesions and AMI are incompletely understood. Calcium-sensing receptors (CaSR) belong to a family of G-protein-coupled receptors. We previously discovered that CaSR was expressed in the heart tissue of adult rats. CaSR may contribute to AMI in AS. We initially established a rat model of AS by injection of vitamin D(3) and feeding with a high-fat diet. Isoproterenol (ISO) was used to induce AMI. The MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), tetrazolium chloride staining, and cardiac function parameters were selected as indicators of myocardial damage or necrosis. Cardiac apoptosis was analyzed by transferase dUTP nick-end labeling (TUNEL) assay. Expression of CaSR, Bcl-2, Bax, caspase-3, p-ERK1/2, p-JNK, and p-p38 were determined by Western blot analysis. Compared with the control group, levels of cTnT, CK-MB, and LDH; number of TUNEL-positive cells; and expression of CaSR, Bax, caspase-3, p-ERK1/2, p-JNK and p-p38, were significantly increased, whereas cardiac function and expression of Bcl-2 were decreased markedly in isoproterenol (ISO)-treated group (C/ISO) and AS groups. These changes were significant in the AS/ISO group than in the C/ISO group or AS group. The upregulation of CaSR during AS formation renders hypersensitivity to AMI. Activation of the pro-apoptotic mitochondria pathway and JNK-p38 MAPK pathway triggered by increased expression of CaSR may be one of molecular mechanisms underlying AMI in AS.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin 150086, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Guo
authors.forename: Hong-Zhu
authors.initials: HZ
authors.lastname: Li
authors.forename: Lu-Chuan
authors.initials: LC
authors.lastname: Wang
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Zhang
authors.forename: Guang-Wei
authors.initials: GW
authors.lastname: Li
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Xing
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Xu
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004198:Disease Susceptibility; D007545:Isoproterenol; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009203:Myocardial Infarction / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D020107:Troponin T / Q000378:metabolism; D015854:Up-Regulation; D016276:Ventricular Function
chemical_list: D051017:Apoptosis Regulatory Proteins; D044169:Receptors, Calcium-Sensing; D014280:Triglycerides; D020107:Troponin T; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases; D052279:Creatine Kinase, MB Form; D007545:Isoproterenol