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Open Access Highly Accessed Original investigation

Progressive decay of Ca2+ homeostasis in the development of diabetic cardiomyopathy

Shu-Mei Zhao, Yong-Liang Wang, Chun-Yan Guo, Jin-Ling Chen and Yong-Quan Wu*

Author Affiliations

Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, XiCheng District, Beijing, China

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Cardiovascular Diabetology 2014, 13:75  doi:10.1186/1475-2840-13-75

Published: 9 April 2014

Abstract

Background

Cardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca2+ homeostasis. This study investigated the effects of alterations in Ca2+ homeostasis and sarcoplasmic reticulum Ca2+-associated proteins on cardiac function in the development of diabetic cardiomyopathy.

Methods

Sprague–Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca2+ spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca2+-associated proteins were assessed by Western blotting.

Results

Echocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca2+ spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca2+ spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca2+-2ATPase (SERCA) and Na+/Ca2+ exchanger (NCX1) were decreased, together with quantitative alterations in Ca2+regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats.

Conclusions

Ca2+ sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca2+-associated proteins.

Keywords:
Spontaneous Ca2+ spark; Cardiac dysfunction; Calcium-associated protein; Diabetic cardiomyopathy