PMID- 7678986 OWN - NLM STAT- MEDLINE DCOM- 19930308 LR - 20220409 IS - 1049-8834 (Print) IS - 1049-8834 (Linking) VI - 13 IP - 2 DP - 1993 Feb TI - An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. PG - 197-204 AB - 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) FAU - Li, H AU - Li H AD - Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital, Boston, MA 02115. FAU - Cybulsky, M I AU - Cybulsky MI FAU - Gimbrone, M A Jr AU - Gimbrone MA Jr FAU - Libby, P AU - Libby P LA - eng GR - HL-34636/HL/NHLBI NIH HHS/United States GR - P01-HL-36028/HL/NHLBI NIH HHS/United States GR - R01-HL-45563/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Arterioscler Thromb JT - Arteriosclerosis and thrombosis : a journal of vascular biology JID - 9101388 RN - 0 (Cell Adhesion Molecules) RN - 0 (Cytokines) RN - 0 (Triglycerides) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Aorta/metabolism MH - Arteriosclerosis/etiology/metabolism MH - Cell Adhesion Molecules/*biosynthesis MH - Cholesterol/blood MH - Cytokines/*pharmacology MH - *Diet, Atherogenic MH - Endothelium, Vascular/*metabolism MH - Male MH - Organ Culture Techniques MH - Rabbits MH - Triglycerides/blood MH - Vascular Cell Adhesion Molecule-1 EDAT- 1993/02/01 00:00 MHDA- 2001/03/28 10:01 CRDT- 1993/02/01 00:00 PHST- 1993/02/01 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1993/02/01 00:00 [entrez] AID - 10.1161/01.atv.13.2.197 [doi] PST - ppublish SO - Arterioscler Thromb. 1993 Feb;13(2):197-204. doi: 10.1161/01.atv.13.2.197.