PMID- 22527939 OWN - NLM STAT- MEDLINE DCOM- 20121009 LR - 20211021 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 366 IP - 1-2 DP - 2012 Jul TI - Increased expression of calcium-sensing receptors in atherosclerosis confers hypersensitivity to acute myocardial infarction in rats. PG - 345-54 LID - 10.1007/s11010-012-1312-0 [doi] AB - 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. FAU - Guo, Jin AU - Guo J AD - Department of Pathophysiology, Harbin Medical University, Harbin 150086, China. FAU - Li, Hong-Zhu AU - Li HZ FAU - Wang, Lu-Chuan AU - Wang LC FAU - Zhang, Wei-Hua AU - Zhang WH FAU - Li, Guang-Wei AU - Li GW FAU - Xing, Wen-Jing AU - Xing WJ FAU - Wang, Rui AU - Wang R FAU - Xu, Chang-Qing AU - Xu CQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120417 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Receptors, Calcium-Sensing) RN - 0 (Triglycerides) RN - 0 (Troponin T) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.3.2 (Creatine Kinase, MB Form) RN - L628TT009W (Isoproterenol) SB - IM MH - Animals MH - Aorta, Abdominal/pathology MH - Apoptosis MH - Apoptosis Regulatory Proteins/metabolism MH - Atherosclerosis/blood/etiology/*metabolism MH - Cholesterol/blood MH - Creatine Kinase, MB Form/blood MH - Diet, High-Fat/adverse effects MH - Disease Susceptibility MH - Isoproterenol MH - L-Lactate Dehydrogenase/blood MH - Male MH - Mitogen-Activated Protein Kinases/metabolism MH - Myocardial Infarction/chemically induced/*metabolism/pathology MH - Myocardium/metabolism/pathology MH - Rats MH - Rats, Wistar MH - Receptors, Calcium-Sensing/genetics/*metabolism MH - Triglycerides/blood MH - Troponin T/metabolism MH - Up-Regulation MH - Ventricular Function EDAT- 2012/04/25 06:00 MHDA- 2012/10/10 06:00 CRDT- 2012/04/25 06:00 PHST- 2011/11/11 00:00 [received] PHST- 2012/04/03 00:00 [accepted] PHST- 2012/04/25 06:00 [entrez] PHST- 2012/04/25 06:00 [pubmed] PHST- 2012/10/10 06:00 [medline] AID - 10.1007/s11010-012-1312-0 [doi] PST - ppublish SO - Mol Cell Biochem. 2012 Jul;366(1-2):345-54. doi: 10.1007/s11010-012-1312-0. Epub 2012 Apr 17.