An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium.
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).(ABSTRACT TRUNCATED AT 250 WORDS)
Li
H
H
Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital, Boston, MA 02115.
Cybulsky
M I
MI
Gimbrone
M A
MA
Libby
P
P
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000494:pharmacology*; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D011817:Rabbits; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D016207:Cytokines; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol