Troglitazone Inhibits Atherosclerosis in Apolipoprotein E–Knockout Mice
- 1 March 2001
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 21 (3), 372-377
- https://doi.org/10.1161/01.atv.21.3.372
Abstract
Abstract —Atherosclerotic coronary heart disease is a common complication of the insulin resistance syndrome that can occur with or without diabetes mellitus. Thiazolidinediones (TZDs), which are insulin-sensitizing antidiabetic agents, can modulate the development of atherosclerosis not only by changing the systemic metabolic conditions associated with insulin resistance but also by exerting direct effects on vascular wall cells that express peroxisome proliferator–activated receptor-γ (PPAR-γ), a nuclear receptor for TZDs. Here we show that troglitazone, a TZD, significantly inhibited fatty streak lesion formation in apolipoprotein E–knockout mice fed a high-fat diet (en face aortic surface lesion areas were 6.9±2.5% vs 12.7±4.7%, P 2 vs 351 738±175 597 μm 2 , P <0.05; n=10). Troglitazone attenuated hyperinsulinemic hyperglycemia and increased high density lipoprotein cholesterol levels. In the aorta, troglitazone markedly increased the mRNA levels of CD36, a scavenger receptor for oxidized low density lipoprotein, presumably by upregulating its expression, at least in part, in the macrophage foam cells. These results indicate that troglitazone potently inhibits fatty streak lesion formation by modulating both metabolic extracellular environments and arterial wall cell functions.Keywords
This publication has 31 references indexed in Scilit:
- Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in miceJCI Insight, 2000
- Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.JCI Insight, 1998
- PPARγ Promotes Monocyte/Macrophage Differentiation and Uptake of Oxidized LDLCell, 1998
- Oxidized LDL Regulates Macrophage Gene Expression through Ligand Activation of PPARγCell, 1998
- Inhibition of oxidation of low density lipoprotein by troglitazoneAtherosclerosis, 1996
- Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects.JCI Insight, 1995
- Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice.JCI Insight, 1994
- Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein EScience, 1992
- Insulin and Atheroma: 20-Yr PerspectiveDiabetes Care, 1990
- High-Density Lipoprotein — The Clinical Implications of Recent StudiesNew England Journal of Medicine, 1989