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Advanced Glycation Endproduct-Induced Calcium Handling Impairment in Mouse Cardiac Myocytes

https://doi.org/10.1006/jmcc.2002.2084Get rights and content

Abstract

R. Petrova, Y. Yamamoto, K. Muraki, H. Yonekura, S. S akurai, T. Watanabe, H. LI, M. Takeuchi, Z. Makita, I. Kato, S. T akasawa, H. Okamoto, Y. Imaizumi and H. Yamamoto. Advanced Glycation Endproduct-Induced Calcium Handling Impairment in Mouse Cardiac Myocytes. Journal of Molecular and Cellular Cardiology (2002) 34, 1425–1431. Long-standing diabetes causes cardiovascular complications including direct cardiac muscle weakening known as diabetic cardiomyopathy. This is characterized by disturbances in both cardiac contraction and relaxation, which are maintained by calcium homeostasis in cardiac cells. Our recent in vitro and in vivo studies have shown that advanced glycation endproducts (AGE) account for diabetic vasculopathy through their engagement of the receptor for AGE (RAGE). Here we show that AGE and RAGE may directly affect the myocardial Ca2+ homeostasis. We created transgenic mice that overexpressed human RAGE in the heart and analyzed the Ca2+ transients in cultivated cardiac myocytes (CM) from the RAGE-transgenic and non-transgenic control fetuses. RAGE overexpression was found to reduce the systolic and diastolic intracellular calcium concentration ([Ca2+]i). Exposure to AGE caused a significant prolongation of the decay time of [Ca2+]i in CM from control mice, and this response was augmented in CM from the RAGE transgenic mice. The results suggest that the AGE and RAGE could play an active role in the development of diabetes-induced cardiac dysfunction.

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f2

On leave from the Second Cardiology Department, St Marina Hospital, Varna, Bulgaria.

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Present address: Department of Biochemistry, Toyama Medical and Pharmaceutical University, Toyama, Japan.

f1

Please address all correspondence to: Hiroshi Yamamoto, MD, PhD, Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Tel: +81-76-265-2180; Fax: +81-76-234-4226; E-mail: [email protected]

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