Dual PPARα/γ Agonist Tesaglitazar Reduces Atherosclerosis in Insulin-Resistant and Hypercholesterolemic ApoE*3Leiden Mice
| Autor: | Louis M. Havekes, Jef J. Emeis, Bart J.M. van Vlijmen, Teake Kooistra, A. Susanne M. Zadelaar, Lianne S.M. Boesten, Germán Camejo, Erik Lundholm, J. Wouter Jukema |
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| Rok vydání: | 2006 |
| Předmět: |
Alkanesulfonates
Apolipoprotein E medicine.medical_specialty Tesaglitazar Apolipoprotein B Lipoproteins medicine.medical_treatment Hypercholesterolemia Apolipoprotein E3 Mice Transgenic Biology Monocytes Cholesterol Dietary Mice chemistry.chemical_compound Apolipoproteins E Internal medicine Cell Adhesion medicine Animals PPAR alpha Serum amyloid A Inflammation Phenylpropionates Cholesterol Macrophages Insulin NF-kappa B Atherosclerosis Dietary Fats Lipids PPAR gamma Endocrinology chemistry biology.protein Blood Vessels Female lipids (amino acids peptides and proteins) Collagen Peroxisome proliferator-activated receptor alpha Insulin Resistance Cardiology and Cardiovascular Medicine Biomarkers Lipoprotein |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 26:2560-2566 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000242904.34700.66 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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