© 2007 European Society of Cardiology
Endogenous inhibitors of hypertrophy in concentric versus eccentric hypertrophy
a University of Antwerp, Laboratory of Physiology Groenenborgerlaan 171, 2020 Antwerp, Belgium
b Department of Cardiac Surgery, Middelheim Hospital Antwerp, Belgium
* Corresponding author. Tel.: +32 3 265 32 77; fax: +32 3 265 32 78. E-mail address: gilles.dekeulenaer{at}ua.ac.be
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Abstract |
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Left ventricular (LV) hypertrophy (LVH) is an adaptive response to hemodynamic overload, but also contributes to the pathogenesis of heart failure. LVH can be concentric (cLVH) but subsequent dilatation and progression to eccentric hypertrophy (eLVH) may lead to global pump failure. Recently, several endogenous molecular inhibitors of hypertrophy have been identified. Using real-time PCR, we compared the myocardial mRNA expression of these inhibitors in pressure-overload induced cLVH (severe aortic stenosis) and in volume overload-induced eLVH (severe mitral regurgitation) in patients, and during the progression from cLVH to eLVH in pressure overload in rat. Each of these genes showed a unique temporal expression profile. Strikingly, except for SOCS-3, changes in gene expression of these negative regulators in rat cLVH and eLVH vs sham were recapitulated in human cLVH and eLVH. In particular, VDUP-1 and MCIP-1 were high in cLVH but expression levels were normal in eLVH, both in rat and human. These data indicate that during the progression of LVH, both in pressure and volume overload, expression levels of endogenous inhibitors of hypertrophy are modified and that these changes may have pathophysiological significance. In particular, MCIP-1 (the endogenous calcineurin inhibitor) and VDUP-1 (the endogenous inhibitor of thioredoxin) are potential molecular switches in the progression of LV hypertrophy.
Key Words: Hypertrophy • gene expression • heart failure • redox
Received April 26, 2006; Revised July 14, 2006; Accepted October 2, 2006