Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high fat fed mice

Tan, Wei Sheng, Mullins, Thomas P., Flint, Melanie, Walton, Sarah L., Bielefeldt-Ohmann, Helle, Carter, David A., Gandhi, Meera R., McDonald, Hayley R., Li, Joan, Moritz, Karen M., Reichelt, Melissa E. and Gallo, Linda A (2018) Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high fat fed mice. American journal of physiology. Regulatory, integrative and comparative physiology, . doi:10.1152/ajpregu.00357.2017


Author Tan, Wei Sheng
Mullins, Thomas P.
Flint, Melanie
Walton, Sarah L.
Bielefeldt-Ohmann, Helle
Carter, David A.
Gandhi, Meera R.
McDonald, Hayley R.
Li, Joan
Moritz, Karen M.
Reichelt, Melissa E.
Gallo, Linda A
Title Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high fat fed mice
Journal name American journal of physiology. Regulatory, integrative and comparative physiology   Check publisher's open access policy
ISSN 1522-1490
0363-6119
Publication date 2018-02-14
Year available 2018
Sub-type Article (original research)
DOI 10.1152/ajpregu.00357.2017
Open Access Status Not yet assessed
Total pages 34
Place of publication Bethesda, MD., United States
Publisher American Physiological Society
Language eng
Abstract There is an increased incidence of heart failure in individuals with diabetes mellitus (DM). The co-existence 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 weeks 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 weeks post-TAC in a separate mouse cohort, echocardiography revealed reduced left ventricular size and increased left ventricular wall thickness; the latter evident in ND mice only. Systolic function was preserved in the TAC mice, and 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.
Keyword cardio-renal
cardiovascular risk
metabolic
obesity
pressure-overload
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 21 Feb 2018, 11:06:28 EST