Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart

Basic Res Cardiol 101: 17 26 (2006)DOI 10.1007/s00395-005-0549-0 ORIGINAL CONTRIBUTIONHans DegensKristel F. J. de BrouwerAndries J. GildeMartijn LindhoutPeter H. M. WillemsenBen J. JanssenGer J. van der VusseMarc van BilsenCardiac fatty acid metabolism is preserved in

the compensated hypertrophic rat heartReceived: 7 June 2005Returned for revision: 27 June 2005

Revision received: 1 August 2005

Accepted: 10 August 2005

Published online: 5 September 2005H. Degens K. F. J. de BrouwerA. J. Gilde M. Lindhout P. H. M. WillemsenG. J. van der Vusse M. van Bilsen, PhD ([L53175])

Dep. of PhysiologyCardiovascular Research Institute Maastricht

(CARIM)Maastricht UniversityPO Box 616

6200 MD Maastricht, the Netherlands

Tel.: [phone]

Fax: [phone]

E-Mail: [email protected]. J. JanssenDep. of Pharmacology

Cardiovascular Research Institute Maastricht

(CARIM)Maastricht UniversityMaastricht, the Netherlands[L52159] Abstract Cardiac hypertrophy and failure are associated with alterations

in cardiac substrate metabolism. It remains to be established, however,

whether genomically driven changes in cardiac glucose and fatty acid (FA)

metabolism represent a key event of the hypertrophic remodeling process.

Accordingly, we investigated metabolic gene expression and substrate metabolism during compensatory hypertrophy, in relation to other cardiac remodeling processes.Thereto, cardiac hypertrophy was induced in rats by supra-renal aortic

constriction to various degrees, resulting in increased heart/body weight

ratios of 22% (Aob-1), 24% (Aob-2) and 32% (Aob-3) (p < 0.005) after 4

weeks. The unaltered ejection fraction in all groups indicated that the hypertrophy was still compensatory in nature. H9252-Myosin Heavy Chain protein and

ANF mRNA levels were increased in all groups. Only in Aob-3 rats were

SERCA2a mRNA levels markedly reduced. In this group, glycolytic capacity

was modestly elevated (+25%; p < 0.01). Notwithstanding these phenotypical changes, the expression of genes involved in FA metabolism and FA oxidation rate in cardiac homogenates was completely preserved, irrespective of

the degree of hypertrophy. These ndings indicate that cardiac FA oxidative

capacity is preserved during compensatory hypertrophy, and that a decline

in metabolic gene expression does not represent a hallmark of the development of hypertrophy.[L52159] Key words metabolism glucose fatty acids gene expression hypertrophy IntroductionCardiac hypertrophy is associated with extensive structural remodeling leading to alterations in myocardial

function [4, 26]. Changes in expression of contractile

protein isoforms, calcium handling proteins and extracellular matrix proteins constitute discrete features of

the hypertrophic remodeling process [7, 13, 30]. Alterations in cardiac energy metabolism...