Frontiers in Physiology | 卷:12 |
Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy | |
Helen Kiriazis1  Alex M. Parker1  Darnel Prakoso1  David M. Nash1  Andrew M. Willis3  Melinda T. Coughlan3  Rebecca H. Ritchie3  Miles J. De Blasio4  Minh Deo6  Mitchel Tate6  Simon Crawford6  Daniel G. Donner6  Cesare Granata8  | |
[1] Diabetes Institute, Melbourne, VIC, Australia; | |
[2] Baker Department of Cardiometabolic Health, The University of Melbourne, Melbourne, VIC, Australia; | |
[3] Baker Heart & | |
[4] Department of Diabetes, Monash University, Melbourne, VIC, Australia; | |
[5] Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, VIC, Australia; | |
[6] Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia; | |
[7] Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia; | |
[8] Ramaciotti Centre for Cryo-Electron Microscopy, Monash University, Melbourne, VIC, Australia; | |
关键词: diabetes; heart; experimental – animal models; mitochondria; diabetic cardiomyopathy; mitochondrial function; | |
DOI : 10.3389/fphys.2021.672252 | |
来源: DOAJ |
【 摘 要 】
People affected by diabetes are at an increased risk of developing heart failure than their non-diabetic counterparts, attributed in part to a distinct cardiac pathology termed diabetic cardiomyopathy. Mitochondrial dysfunction and excess reactive oxygen species (ROS) have been implicated in a range of diabetic complications and are a common feature of the diabetic heart. In this study, we sought to characterise impairments in mitochondrial structure and function in a recently described experimental mouse model of diabetic cardiomyopathy. Diabetes was induced in 6-week-old male FVB/N mice by the combination of three consecutive-daily injections of low-dose streptozotocin (STZ, each 55 mg/kg i.p.) and high-fat diet (42% fat from lipids) for 26 weeks. At study end, diabetic mice exhibited elevated blood glucose levels and impaired glucose tolerance, together with increases in both body weight gain and fat mass, replicating several aspects of human type 2 diabetes. The myocardial phenotype of diabetic mice included increased myocardial fibrosis and left ventricular (LV) diastolic dysfunction. Elevated LV superoxide levels were also evident. Diabetic mice exhibited a spectrum of LV mitochondrial changes, including decreased mitochondria area, increased levels of mitochondrial complex-III and complex-V protein abundance, and reduced complex-II oxygen consumption. In conclusion, these data suggest that the low-dose STZ-high fat experimental model replicates some of the mitochondrial changes seen in diabetes, and as such, this model may be useful to study treatments that target the mitochondria in diabetes.
【 授权许可】
Unknown