Premium
Very long chain acyl‐CoA dehydrogenase (VLCAD) null mouse hearts display a prolonged QTc interval and low docosahexaenoic acid levels
Author(s) -
Gélinas Roselle,
ThompsonLegault Julie,
Bouchard Bertrand,
Daneault Caroline,
Gillis MarcAntoine,
Labarthe François,
DesRosiers Christine
Publication year - 2011
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.25.1_supplement.722.3
Patients with fatty acid oxidation (FAO) defects develop cardiomyopathy, yet the underlying mechanisms are unclear. In this study we have tested for metabolic and functional alterations in hearts from VLCAD deficient (VLCAD −/− ) mice using both (i) ex vivo perfusion in the working mode with 13 C‐labeled substrates and (ii) in vivo targeted lipidomic and gene expression analysis of heart tissues as well as ECG monitoring by telemetry. When perfused ex vivo , hearts from 7 month‐old fed VLCAD −/− mouse displayed similar physiological and metabolic parameters compared to control VLCAD +/+ counterparts, even at high FA concentration. This suggested a compensatory mechanism, a notion that was supported by gene expression data revealing little or no difference in the transcript level for Acadl, another long chain FAO enzyme between VLCAD −/− and control hearts. However, VLCAD −/− hearts displayed in vivo a ~15% (p<0.05) prolonged QTc interval which was associated with the following lipid alterations: (i) age‐ and condition‐dependent accumulation of triglycerides and (ii) a 20% lower level of docosahexaenoic acid (DHA) in phospholipids. Our finding of decrease in DHA in VLCAD −/− hearts appears of specific relevance to the development of electrical abnormalities, specifically the longer QTc interval, a condition that predisposes to sudden cardiac death. (Supported by NIH & CIHR)