Progressive decay of Ca2+ homeostasis in the development of diabetic cardiomyopathy.
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.
Shu-Mei
SM
Zhao
Yong-Liang
YL
Wang
Chun-Yan
CY
Guo
Jin-Ling
JL
Chen
Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Road, XiCheng District, Beijing, China. yd678182@163.com.
Yong-Quan
YQ
Wu
D000818:Animals; D002118:Calcium / Q000502:physiology*; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging* / Q000378:metabolism*; D018450:Disease Progression; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
D002118:Calcium