Print Email Facebook Twitter Dual PPARα/γ agonist tesaglitazar reduces atherosclerosis in insulin-resistant and hypercholesterolemic ApoE*3Leiden mice Title Dual PPARα/γ agonist tesaglitazar reduces atherosclerosis in insulin-resistant and hypercholesterolemic ApoE*3Leiden mice Author Zadelaar, A.S.M. Boesten, L.S.M. Jukema, J.W. van Vlijmen, B.J.M. Kooistra, T. Emeis, J.J. Lundholm, E. Camejo, G. Havekes, L.M. Gaubius Instituut TNO Publication year 2006 Abstract OBJECTIVE - We investigated whether the dual PPARα/γ agonist tesaglitazar has anti-atherogenic effects in ApoE*3Leiden mice with reduced insulin sensitivity. METHODS AND RESULTS - ApoE*3Leiden transgenic mice were fed a high-fat (HF) insulin-resistance-inducing diet. One group received a high-cholesterol (HC) supplement (1% wt/wt; HC group). A second group received the same HC supplement along with tesaglitazar (T) 0.5 μmol/kg diet (T group). A third (control) group received a low-cholesterol (LC) supplement (0.1% wt/wt; LC group). Tesaglitazar decreased plasma cholesterol by 20% compared with the HC group; cholesterol levels were similar in the T and LC groups. Compared with the HC group, tesaglitazar caused a 92% reduction in atherosclerosis, whereas a 56% reduction was seen in the cholesterol-matched LC group. Furthermore, tesaglitazar treatment significantly reduced lesion number beyond that expected from cholesterol lowering and induced a shift to less severe lesions. Concomitantly, tesaglitazar reduced macrophage-rich and collagen areas. In addition, tesaglitazar reduced inflammatory markers, including plasma SAA levels, the number of adhering monocytes, and nuclear factor κB-activity in the vessel wall. CONCLUSIONS - Tesaglitazar has anti-atherosclerotic effects in the mouse model that go beyond plasma cholesterol lowering, possibly caused by a combination of altered lipoprotein profiles and anti-inflammatory vascular effects. © 2006 American Heart Association, Inc. Chemicals / CAS: cholesterol, 57-88-5; collagen, 9007-34-5; tesaglitazar, 251565-85-2; lipid, 66455-18-3; peroxisome proliferator activated receptor alpha, 147258-70-6; 2-ethoxy-3-(4-((4-(methylsulfonyloxy)phenethyl)oxy)phenyl)propanoic acid; Alkanesulfonates; apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins E; Biological Markers; Cholesterol, 57-88-5; Cholesterol, Dietary; Collagen, 9007-34-5; Dietary Fats; Lipids; Lipoproteins; NF-kappa B; Phenylpropionates; PPAR alpha; PPAR gamma Subject CholesterolInhibitorsCollagenImmunoglobulin enhancer binding proteinSerum amyloid ATesaglitazar2 ethoxy 3 (4 ((4 (methylsulfonyloxy)phenethyl)oxy)phenyl)propanoic acidAlkanesulfonic acidApolipoprotein E3 (Leidein)Biological markerLipoproteinPeroxisome proliferator activated receptor alphaPeroxisome proliferator activated receptor gammaPhenylpropionic acid derivativeAnimal cellAnimal experimentAnimal modelAnimal tissueBlood vessel wallCholesterol blood levelControlled studyDietEnzyme activityMonocyteMouseNonhumanProtein blood levelTransgenic mouseBloodCholesterol intakeDrug potentiationFat intakeMetabolismPathologyPathophysiologyAlkanesulfonatesAnimalsApolipoprotein E3Apolipoproteins EAtherosclerosisBiological MarkersBlood VesselsCell AdhesionCholesterolCholesterol, DietaryCollagenDietary FatsFemaleHypercholesterolemiaInflammationInsulin ResistanceLipidsLipoproteinsMacrophagesMiceMice, TransgenicMonocytesNF-kappa BPhenylpropionatesPPAR alphaPPAR gamma To reference this document use: http://resolver.tudelft.nl/uuid:39ea62fc-bb35-4e7e-a021-8e81d3e6e011 DOI https://doi.org/10.1161/01.atv.0000242904.34700.66 TNO identifier 239560 ISSN 1079-5642 Source Arteriosclerosis, Thrombosis, and Vascular Biology, 26 (11), 2560-2566 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.