title: Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy.
abstract: Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δ overexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δ induces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δ activation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease.
authors.affiliation: Institute of Biology Valrose (iBV), University of Nice Sophia Antipolis, CNRS UMR7277/INSERM U1091, Faculty of Medicine, 06107 Nice, France.
authors.forename: Kay-Dietrich
authors.initials: KD
authors.lastname: Wagner
authors.affiliation: Institute for Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Ana
authors.initials: A
authors.lastname: Vukolic
authors.affiliation: Institute of Biology Valrose (iBV), University of Nice Sophia Antipolis, CNRS UMR7277/INSERM U1091, Faculty of Medicine, 06107 Nice, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Baudouy
authors.affiliation: Department of Pathology, CHU Nice, 06002 Nice, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.affiliation: Institute of Biology Valrose (iBV), University of Nice Sophia Antipolis, CNRS UMR7277/INSERM U1091, Faculty of Medicine, 06107 Nice, France.
authors.forename: Nicole
authors.identifier: 0000-0002-2746-0707
authors.initials: N
authors.lastname: Wagner