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Acta Physiologica 2005; Volume 185, Supplement 649
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Autumn Meeting 2005
11/19/2005-11/19/2005
Antwerp, Belgium
EXPRESSION OF NEGATIVE REGULATORS OF HYPERTROPHY IN CONCENTRIC AND ECCENTRIC HYPERTROPHY OF RAT AND HUMAN LEFT VENTRICLES
Abstract number: ORAL-4
Lemmens K., Segers V.F.M., Demolder M., Michiels M., Muylaert P., De Worm E., Van Cauwelaert P., De Keulenaer G.W.
Laboratory of Physiology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium
Introduction:
Concentric and eccentric left ventricular (LV) hypertrophy (LVH) are adaptive responses of the heart to pressure and volume overload, but also represent intermediate steps toward myocardial dysfunction and failure. The pathways promoting hypertrophy have been extensively studied. More recently, negative feedback regulators of these pathways have been identified. Interestingly, expression of these negative regulators of hypertrophy is influenced by mechanical strain. However their physiological relevance is poorly understood.
Methods:
We screened the expression of 5 suppressors of hypertrophic pathways (IEX-1, MKP-1, SOCS-3, VDUP-1 and MCIP-1) in a rat model of transverse aortic constriction (TAC) and in human concentric or eccentric LVH ("thru-cut" LV biopsies during surgery for severe aortic stenosis and severe mitral regurgitation). Expression of genes was assessed at mRNA level with real-time PCR. Sham-operated rats and surgical biopsies from non-hypertrophied human LV served as controls.
Results:
LV pressure overload in the rat induced concentric LVH at 8 weeks, but eccentric LVH with reduced fractional shortening at 16 weeks of TAC. Each of the genes followed a unique temporal expression profile during these 16 weeks. Interestingly, the expression levels of 3 genes (MCIP1, VDUP-1, SOCS-3) robustly switched upon transition from concentric to eccentric LVH (for MCIP-1, see figure A). In the human LV biopsies, a similar differential expression between concentric and eccentric LVH was only observed for MCIP1 (figure B). The expression of the other genes was not significantly different in concentric and eccentric human LVH.
Conclusion:
Gene activity of MCIP1 (an inhibitory calcineurin-interacting protein), but not the gene activity of other suppressors of hypertrophy, differs between human concentric and eccentric LVH. Disturbances of specific inhibitory pathways, rather than a general impairment of negative feedback systems may differentiate concentric and eccentric LVH, and the transition from one to the other.
To cite this abstract, please use the following information:
Acta Physiologica 2005; Volume 185, Supplement 649 :ORAL-4