AN ATHEROGENIC DIET RAPIDLY INDUCES VCAM-1, A CYTOKINE-REGULATABLE MONONUCLEAR LEUKOCYTE ADHESION MOLECULE, IN RABBIT AORTIC ENDOTHELIUM
AN ATHEROGENIC DIET RAPIDLY INDUCES VCAM-1, A CYTOKINE-REGULATABLE MONONUCLEAR LEUKOCYTE ADHESION MOLECULE, IN RABBIT AORTIC ENDOTHELIUM
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DOI：
10.1161/01.atv.13.2.197
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发表时间：
1993-02-01
期刊：
影响因子：
--
通讯作者：
LIBBY, P
中科院分区：
文献类型：
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作者：
LI, H;CYBULSKY, MI;LIBBY, P
单核细胞源性泡沫细胞在动脉内膜局灶性区域的积聚是早期动脉粥样硬化形成的关键步骤。我们研究了血管细胞粘附分子-1（VCAM-1）的表达，单核白细胞粘附分子，在动脉内皮在早期阶段的饮食诱导的动脉粥样硬化在兔体内和调节VCAM-1表达的细胞因子在兔主动脉类器官体外培养。给家兔喂食致动脉粥样硬化饮食（含0.3%胆固醇、9%椰子油和1%玉米油）或等热量对照饮食（10%玉米油）4天或1、3、6或13周。通过连续切片的免疫组化染色判断，在致动脉粥样硬化饮食仅1周后，但在内膜巨噬细胞首次出现之前，升主动脉中的内皮局部表达VCAM-1。食用致动脉粥样硬化饮食3周或更长时间的家兔在内膜中出现由携带II类主要组织相容性抗原（MHC-II）的巨噬细胞组成的病变。内皮细胞继续在MHC-II阳性内膜巨噬细胞的部位局部表达VCAM-1长达13周。对照组家兔的升支动脉在所有研究时间均缺乏VCAM-1或MHC-II阳性内皮细胞或巨噬细胞。这些观察结果表明，早在开始致动脉粥样硬化饮食（血清胆固醇水平为308+/-57 mg/dl）后7天，动脉内皮就出现局灶性活化。在兔胸主动脉的类器官培养物中，革兰氏阴性细菌脂多糖或细胞因子白细胞介素（IL）-1 α、肿瘤坏死因子-α和IL-4以及干扰素γ诱导内皮细胞VCAM-1表达。我们的研究结果表明，精氨酸诱导的内皮功能的激活，如VCAM-1的表达，可能参与了饮食诱导的动脉粥样硬化的开始在兔。
Accumulation of monocyte-derived foam cells in focal areas of the arterial intima is a key step in early atherogenesis. We investigated the expression of vascular cell adhesion molecule-1 (VCAM-1), a mononuclear leukocyte adhesion molecule, in the arterial endothelium during the early phases of diet-induced atherogenesis in rabbits in vivo and the regulation of VCAM-1 expression by cytokines in rabbit aortic organoid cultures in vitro. Rabbits were fed either an atherogenic diet (containing 0.3% cholesterol, 9% coconut oil, and 1% corn oil) or an isocaloric control diet (10% corn oil) for 4 days or 1, 3, 6, or 13 weeks. The endothelium in the ascending aorta focally expressed VCAM-1 after only 1 week on the atherogenic diet but before the first appearance of intimal macrophages, as judged by immunohistochemical staining of serial sections. The rabbits that consumed the atherogenic diet for 3 weeks or longer developed lesions in the intima composed of macrophages bearing class II major histocompatibility antigen (MHC-II). Endothelial cells continued to focally express VCAM-1 at sites of MHC-II-positive intimal macrophages for up to 13 weeks. The ascending aortas of control rabbits lacked VCAM-1 or MHC-II-positive endothelium or macrophages at all times studied. These observations demonstrate the focal activation of arterial endothelium as early as 7 days after initiation of an atherogenic diet (at serum cholesterol levels of 308+/-57 mg/dl). In organoid cultures of rabbit thoracic aortas, Gram-negative bacterial lipopolysaccharide or the cytokines interleukin (IL)-1alpha, tumor necrosis factor-alpha, and IL-4, as well as interferon gamma, induced VCAM-1 expression in the endothelium. Our results suggest that the activation of cytokine-inducible endothelial functions, such as expression of VCAM-1, may participate in the initiation of diet-induced atherosclerosis in rabbits.