Premium
Cardiomyocyte‐Specific Ablation of the Long‐Chain Fatty Acid Transporter CD36 Accelerates the Progression of Pressure Overload‐Induced Heart Failure in Mice
Author(s) -
Sung Miranda,
Byrne Nikole,
Levasseur Jody,
Masson Grant,
Febbraio Maria,
Dyck Jason
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb593
Subject(s) - cd36 , pressure overload , fatty acid , beta oxidation , medicine , endocrinology , heart failure , transporter , muscle hypertrophy , chemistry , biochemistry , cardiac hypertrophy , receptor , gene
Utilizing an inducible cardiomyocyte‐specific CD36 knockout (icCD36KO) mouse, we investigated the pathophysiological role of myocardial fatty acid transporter CD36 in response to pressure overload and tested whether the ablation of CD36, used as a tool to limit fatty acid uptake and partially inhibit fatty acid oxidation, would be beneficial or detrimental to cardiac function. Wildtype (WT) and icCD36KO mice were subjected to transverse aortic constriction (TAC) surgery to generate pressure overload‐induced cardiac hypertrophy. Following TAC, both WT and icCD36KO mice developed similar degrees of compensatory cardiac hypertrophy in response to pressure overload at 1, 3 and 5 weeks post‐TAC (N=7‐11/group). However, we observed significant systolic dysfunction and reduced ejection fraction (EF) in icCD36KO mice at 5 weeks post‐TAC (%EF: 52.4 ± 2.82 vs. 35.6 ± 3.01; P<0.05). Prior to TAC, cardiac fatty acid oxidation rates were significantly reduced and glucose oxidation rates increased in hearts from icCD36KO compared to WT mice. However, at 5 weeks post‐TAC both glucose and fatty acid oxidation rates were reduced to a similar extent in both WT and icCD36KO mice (N=4). Interestingly, icCD36KO mice fed a diet rich in medium chain fatty acids, which do not require CD36 as a transporter to enter the cardiomyocyte, were protected from TAC‐induced systolic dysfunction (%EF: 45.2 ± 2.67, N=5). In conclusion, these data suggest that limiting fatty acid uptake and partial inhibition of fatty acid oxidation in the heart via CD36 ablation may be detrimental, at least early on during the development of pressure overload‐induced HF.