Journal article
Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high-fat-fed mice
AJP: Regulatory, Integrative and Comparative Physiology, Vol.314(6), pp.R858-R869
2018
PMID: 29443547
Abstract
There is an increased incidence of heart failure in individuals with diabetes mellitus (DM). The coexistence of kidney disease in DM exacerbates the cardiovascular prognosis. Researchers have attempted to combine the critical features of heart failure, using transverse aortic constriction, with DM in mice, but variable findings have been reported. Furthermore, kidney outcomes have not been assessed in this setting; thus its utility as a model of heart failure in DM and kidney disease is unknown. We generated a mouse model of obesity, hyperglycemia, and mild kidney pathology by feeding male C57BL/6J mice a high-fat diet (HFD). Cardiac pressure overload was surgically induced using transverse aortic constriction (TAC). Normal diet (ND) and sham controls were included. Heart failure risk factors were evident at 8-wk post-TAC, including increased left ventricular mass (+49% in ND and +35% in HFD), cardiomyocyte hypertrophy (+40% in ND and +28% in HFD), and interstitial and perivascular fibrosis (Masson's trichrome and picrosirius red positivity). High-fat feeding did not exacerbate the TAC-induced cardiac outcomes. At 11 wk post-TAC in a separate mouse cohort, echocardiography revealed reduced left ventricular size and increased left ventricular wall thickness, the latter being evident in ND mice only. Systolic function was preserved in the TAC mice and was similar between ND and HFD. Thus combined high-fat feeding and TAC in mice did not model the increased incidence of heart failure in DM patients. This model, however, may mimic the better cardiovascular prognosis seen in overweight and obese heart failure patients.
Details
- Title
- Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high-fat-fed mice
- Authors
- Wei Sheng Tan (Author) - University of QueenslandThomas P Mullins (Author) - University of QueenslandMelanie Flint (Author) - University of QueenslandSarah L Walton (Author) - University of QueenslandHelle Bielefeldt-Ohmann (Author) - University of QueenslandDavid A Carter (Author) - University of QueenslandMeera R Gandhi (Author) - University of QueenslandHayley R McDonald (Author) - University of QueenslandJoan Li (Author) - Australian Institute for Bioengineering and Nanotechnology, The University of Queensland , St. Lucia , AustraliaKaren M Moritz (Author) - University of QueenslandMelissa E Reichelt (Author) - University of QueenslandLinda A Gallo (Author) - University of Queensland
- Publication details
- AJP: Regulatory, Integrative and Comparative Physiology, Vol.314(6), pp.R858-R869
- Publisher
- American Physiological Society
- DOI
- 10.1152/ajpregu.00357.2017
- ISSN
- 1522-1490
- PMID
- 29443547
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy; School of Health - Biomedicine
- Language
- English
- Record Identifier
- 99620607402621
- Output Type
- Journal article
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- Domestic collaboration
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- Physiology
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