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Increased expression of calcium-sensing receptors in atherosclerosis confers hypersensitivity to acute myocardial infarction in rats

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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 D3 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.

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Acknowledgments

This work was supported by the National Basic Research Program of China (973 Program, grant number 2007CB512000); National Natural Science Foundation of China (number 30871012,81000059 and 30700288); Youth Fund of Jiamusi University (number Sq2011-025).

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Authors and Affiliations

  1. Department of Pathophysiology, Harbin Medical University, Harbin, 150086, China

    Jin Guo, Hong-zhu Li, Wei-hua Zhang, Guang-wei Li, Wen-jing Xing, Rui Wang & Chang-qing Xu

  2. Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, 150086, China

    Wei-hua Zhang & Chang-qing Xu

  3. Department of Cerebral Palsy, Tertiary Hospital of Jiamusi University, Jiamusi, 154003, China

    Jin Guo

  4. Department of Orthopaedics, First Hospital of Jiamusi University, Jiamusi, 154003, China

    Lu-chuan Wang

  5. Department of Biology, Lakehead University, Thunder Bay, ON, P7B5E1, Canada

    Rui Wang

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  1. Jin Guo
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Correspondence to Chang-qing Xu.

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Jin Guo and Hong-zhu Li—co-first authors.

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Guo, J., Li, Hz., Wang, Lc. et al. Increased expression of calcium-sensing receptors in atherosclerosis confers hypersensitivity to acute myocardial infarction in rats. Mol Cell Biochem 366, 345–354 (2012). https://doi.org/10.1007/s11010-012-1312-0

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  • DOI: https://doi.org/10.1007/s11010-012-1312-0

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