期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：11
页码：6730-6735
DOI：10.1073/pnas.1137612100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Hyperlipidemia promotes the chronic inflammatory disease atherosclerosis through poorly understood mechanisms. Atherogenic lipoproteins activate platelets, but it is unknown whether platelets contribute to early inflammatory atherosclerotic lesions. To address the role of platelet aggregation in diet-induced vascular disease, we studied {beta}3 integrin-deficient mice (lacking platelet integrin IIb{beta}3 and the widely expressed nonplatelet integrin v{beta}3) in two models of atherosclerosis, apolipoprotein E (apoE)-null and low-density lipoprotein receptor (LDLR)-null mice. Unexpectedly, a high-fat, Western-type (but not a low-fat) diet caused death in two-thirds of the {beta}3-/-apoE-/- and half of the {beta}3-/-LDLR-/- mice due to noninfectious pneumonitis. In animals from both models surviving high-fat feeding, pneumonitis was absent, but aortic atherosclerosis was 2- to 6-fold greater in {beta}3-/- compared with {beta}+/+ littermates. Expression of CD36, CD40L, and CD40 was increased in lungs of {beta}3-/-LDLR-/- mice. Each was also increased in smooth muscle cells cultured from {beta}3-deficient mice and suppressed by retroviral reconstitution of {beta}3. These data show that the platelet defect caused by IIb{beta}3 deficiency does not impair atherosclerotic lesion initiation. They also suggest that v{beta}3 has a suppressive effect on inflammation, the loss of which induces atherogenic mediators that are amplified by diet-induced hyperlipidemia.
