Diastolic dysfunction in spontaneous type 2 diabetes rhesus monkeys: a study using echocardiography and magnetic resonance imaging

BMC Cardiovascular Disorders

Research Article

Wei Chen¹  Bing Wu¹  Fabao Gao¹  Ziqian Xu¹  Yushu Chen¹  Chungui Tang²  Can Qian³  Wen Zeng³  Zunyuan Yang⁴  Li Gong⁴ 

[1] Department of Radiology, West China Hospital, Sichuan University, Chengdu, China;Department of Radiology, Yaan People’s Hospital, Yaan, China;Sichuan Industrial Institute of Antibiotics, Chengdu, China;Sichuan PriMed Shines Bio-Tech Co., Ltd, Chengdu, China;Sichuan PriMed Shines Bio-Tech Co., Ltd, Chengdu, China;

关键词: Fast Plasma Glucose;    Cardiac Magnetic Resonance;    Diastolic Dysfunction;    Tissue Doppler Imaging;    Diabetic Cardiomyopathy;   

DOI  :  10.1186/s12872-015-0046-9

 received in 2015-02-04, accepted in 2015-06-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundDiastolic heart failure is a common and deadly complication of diabetes mellitus, with the development of diabetic cardiomyopathy as one of the key determinants of the disease’s complex pathology. The cause of the association is unknown and has no approved therapy strategies as of yet. However significant advances in this area may come from studies on suitable animal models.MethodsA total of 25 male rhesus monkeys (12-16 years, 9-13 kg) were enrolled. Fifteen of them were diagnosed as spontaneous type 2 diabetes mellitus (T2DM, FPG ≥ 104 mg/dl, HbA1c: 4.7-5.5 %, diabetes duration: 1-4 years). The other 10 monkeys were non-diabetic (ND, FPG < 90 mg/dl). Echocardiography and cardiac magnetic resonance were used for evaluating the cardiac structure and function. One T2DM monkey with impaired diastolic function and another ND monkey were both sacrificed to gain the necessary pathology and protein expression studies displayed here.ResultsSix out of 15 T2DM rhesus monkeys were diagnosed with diastolic dysfunction (DD) by echocardiography. Additionally, no abnormalities were found in the group which we determined as the ND monkeys. The six DD monkeys all showed low e’ velocity and decreased e’/a’ ratio, among which three of them showing decreased E/A ratio and the other 3 having elevated E/A ratio, this appears to be similar to the impaired relaxation pattern and pseudonormal pattern found in human patients respectively. The EF and FS of monkeys with pseudonormal pattern decreased significantly compared with ND subjects. A CMR study showed that LVID at end systole of 5 DD monkeys is significantly longer than that of 3 ND monkeys. Of great interest, myocardium lesions and mitochondria impairments and increased expression of AGEs and caspase-3 were found in a sacrificed DD subject.ConclusionThe changes in the imaging and physiological markers of spontaneous T2DM rhesus monkeys are similar to those key markers found in human type 2 diabetes and diastolic dysfunction. This monkey model could help the medical community and us to understand the pathology of this debilitating disease and serve as a beginning to explore important measures to prevent and treat diabetic cardiomyopathy.

【 授权许可】

Unknown   
© Qian et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.