PMID- 26879576 OWN - NLM STAT- MEDLINE DCOM- 20160823 LR - 20211103 IS - 1471-2261 (Electronic) IS - 1471-2261 (Linking) VI - 16 DP - 2016 Feb 16 TI - Left ventricular deformation associated with cardiomyocyte Ca(2+) transients delay in early stage of low-dose of STZ and high-fat diet induced type 2 diabetic rats. PG - 41 LID - 10.1186/s12872-016-0220-8 [doi] LID - 41 AB - BACKGROUND: In the early stage of diabetes, the cardiac ejection fraction is preserved, despite the existence of the subclinical cardiac dysfunction to some extent. However, the detailed phenotype of this dysfunction and the underlying mechanism remain unclear. To improve our understanding of this issue, we used low-dose STZ and high-fat diet to induce type 2 diabetic models in rats. The effects and the mechanism associated with the early stages of the disease were analyzed. METHODS: The type 2 diabetic mellitus (T2DM) in SD rats were induced through 30 mg/kg STZ and high-fat diet. Two-dimensional spackle-tracking echocardiography (STE) and the dobutamine test were performed to examine the cardiac function. Calcium transients of left ventricular myocytes were detected and the related intracellular signalling factors were analyzed by western blotting. RESULTS: After 6-weeks, T2DM rats in left ventricular (LV) diastole showed decreased global and segment strain(S) levels (P < 0.05), both in the radial and circumferential directions. Strain rate (Sr) abatement occurred in three segments in the radial and circumferential directions (P < 0.05), and the radial global Sr also decreased (P < 0.05). In the systolic LV, radial Sr was reduced, except the segment of the anterior septum, and the Sr of the lateral wall and post septum decreased in the circumferential direction (P < 0.05). Conventional M-mode echocardiography failed to detect significant alterations of cardiac performance between the two groups even after 12 weeks, and the decreased ejection fraction (EF%), fractional shortening (FS%) and end-systolic diameters (ESD) could be detected only under stress conditions induced by dobutamine (P < 0.05). In terms of calcium transients in cardiac myocytes, the Tpeak in model rats at 6 weeks was not affected, while the Tdecay1/2 was higher than that of the controls (P < 0.05), and both showed a dose-dependent delay after isoproterenol treatment (P < 0.05). Western blot analysis showed that in 6-week T2DM rats, myocardial p-PLB expression was elevated, whereas p-CaMKII, p-AMPK and Sirt1 were significantly down-regulated (P < 0.05). CONCLUSION: A rat model of T2DM was established by low dose STZ and a high-fat diet. LV deformation was observed in the early stages of T2DM in association with the delay of Ca(2+) transients in cardiomyocytes due to the decreased phosphorylation of CaMKII. Myocardial metabolism remodeling might contribute to the early LV function and calcium transportation abnormalities. FAU - Liu, Xiao-Ying AU - Liu XY AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Liu, Fu-Cheng AU - Liu FC AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. AD - Department of Cardiology of the First Affiliated Hospital, Jinan University, Guangzhou, 510630, P.R. China. FAU - Deng, Chun-Yu AU - Deng CY AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Zhang, Meng-Zhen AU - Zhang MZ AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Yang, Min AU - Yang M AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Xiao, Ding-Zhang AU - Xiao DZ AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Lin, Qiu-Xiong AU - Lin QX AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Cai, Shi-Ting AU - Cai ST AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Kuang, Su-Juan AU - Kuang SJ AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Chen, Jing AU - Chen J AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Chen, Shao-Xian AU - Chen SX AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Zhu, Jie-Ning AU - Zhu JN AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Yang, Hui AU - Yang H AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Rao, Fang AU - Rao F AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Fu, Yong-Heng AU - Fu YH AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. FAU - Yu, Xi-Yong AU - Yu XY AD - Guangdong Cardiovascular Institute and Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, P.R. China. yuxycn@aliyun.com. AD - Institute of Molecular and Clinical Pharmacology, Guangzhou Medical University, Guangzhou, 511436, P.R. China. yuxycn@aliyun.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160216 PL - England TA - BMC Cardiovasc Disord JT - BMC cardiovascular disorders JID - 100968539 RN - 0 (Calcium-Binding Proteins) RN - 0 (Phosphoproteins) RN - 0 (phospholamban) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.5.1.- (Sirt1 protein, rat) RN - EC 3.5.1.- (Sirtuin 1) RN - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Animals MH - Blotting, Western MH - Calcium/*metabolism MH - Calcium-Binding Proteins/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism MH - Diabetes Mellitus, Experimental/complications/*metabolism MH - Diabetes Mellitus, Type 2/complications/*metabolism MH - Diabetic Cardiomyopathies/diagnostic imaging/etiology/*metabolism MH - *Diet, High-Fat MH - Disease Models, Animal MH - Echocardiography MH - Echocardiography, Stress MH - Electrophoresis, Polyacrylamide Gel MH - Heart Ventricles/cytology/diagnostic imaging/*metabolism MH - Immunoblotting MH - Myocytes, Cardiac/*metabolism MH - Phosphoproteins/metabolism MH - Rats MH - Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism MH - Sirtuin 1/metabolism PMC - PMC4754853 EDAT- 2016/02/18 06:00 MHDA- 2016/08/24 06:00 PMCR- 2016/02/16 CRDT- 2016/02/17 06:00 PHST- 2015/07/20 00:00 [received] PHST- 2016/02/09 00:00 [accepted] PHST- 2016/02/17 06:00 [entrez] PHST- 2016/02/18 06:00 [pubmed] PHST- 2016/08/24 06:00 [medline] PHST- 2016/02/16 00:00 [pmc-release] AID - 10.1186/s12872-016-0220-8 [pii] AID - 220 [pii] AID - 10.1186/s12872-016-0220-8 [doi] PST - epublish SO - BMC Cardiovasc Disord. 2016 Feb 16;16:41. doi: 10.1186/s12872-016-0220-8.