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Acta Physiologica 2007; Volume 191, Supplement 658
Joint Meeting of The Slovak Physiological Society, The Physiological Society and The Federation of European Physiological Societies
9/11/2007-9/14/2007
Bratislava, Slovakia
DELETION OF PPAR RESULTS IN MORE PRONOUNCED CARDIAC HYPERTROPHY IN RESPONSE TO CHRONIC PRESSURE OVERLOAD
Abstract number: OTH09-35
Teunissen1 B.E.J., Smeets1 P.J.H., Willemsen1 P.H., Brouns1 A.E., Janssen1 B.J., van der Vusse1 G.J., van Bilsen1 M.
1Department of Physiology, CARIM, Maastricht University, The Netherlands [email protected]
Aim:
Peroxisome proliferator-activated receptor-a (PPARa) is a nuclear receptor regulating cardiac metabolism and has anti-inflammatory as well as anti-fibrotic effects. Given these properties it is anticipated that PPARa modulates cardiac remodeling. Therefore, we studied the role of PPARa in pressure-overload induced hypertrophy.
Methods and Results:
PPARa-/- (KO) and PPARa+/+ (WT) mice were subjected to transverse aortic constriction (TAC) for 28 days. Sham-operated KO and WT mice served as controls (N >= 9 in all groups). KO mice had slightly lower blood pressure than WT mice (111 vs. 122 mmHg, p < 0.05). Nevertheless, TAC resulted in more pronounced posterior and anterior left ventricular (LV) wall thickness and LV/body weight ratio in KO-TAC than in WT-TAC (LVW/BW: +37% vs. +20%, p < 0.05). LV ejection fraction and maximal LV contractility (+dP/ dtmax) were significantly lower in KO-TAC compared to sham (-19.4% and -19.2%, respectively, p < 0.05), but not in WT-TAC. Moreover, in KO-TAC mice LV mRNA levels of hypertrophic (ANF), fibrotic (Collagen 1, MMP-2) and inflammatory (Interleunited kingdomin-6, TNF-a) genes were significantly higher relative to WT-TAC.
Conclusion:
Absence of PPARa results in a more pronounced hypertrophic growth response, indicating that PPARa attenuates pathological cardiac remodeling following pressure overload.
Supported by grants EU No. LSHM-CT-2005-018833/EUGeneHeart and NWO No. 912-04-017.
To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 191, Supplement 658 :OTH09-35