title: Hypercholesterolemia alters endotoxin-induced endothelial cell adhesion molecule expression.
abstract: While there is a growing body of evidence suggesting that hypercholesterolemia prior to the onset of atherosclerosis renders tissues more susceptible to inflammation, the mechanisms that underlie this exaggerated inflammatory response remain poorly defined. The overall objective of this study was to assess the influence of hypercholesterolemia on endotoxin-induced endothelial cell adhesion molecule (CAM) expression in different vascular beds. Another objective was to determine whether the altered endothelial CAM expression in hypercholesterolemic animals is associated with a corresponding change in plasma cytokine levels. Male Sprague/Dawley rats (SD) were placed either on a normal (control) or high cholesterol (HC) diet for 3 weeks. The dual radiolabeled monoclonal antibody (mAb) technique was used to measure the expression of P-selectin, E-selectin, ICAM-1, and VCAM-1 in different vascular beds after intraperitoneal injection of endotoxin (LPS) derived from Salmonella abortus equi. LPS induced a significant increase in the expression of all endothelial CAMs in both normocholesterolemic and hypercholesterolemic groups. However, hypercholesterolemia enhanced LPS-induced expression of P-selectin, E-selectin, and ICAM-1 in several vascular beds, while VCAM-1 expression was unaffected. Thrombocytopenia, induced with anti-platelet serum, did not alter LPS-induced P-selectin expression in either group, suggesting that platelets do not contribute to this response. Hypercholesterolemia was associated with an exaggerated increase in plasma TNF-alpha, but not IL-1beta, after LPS treatment. These results indicate that hypercholesterolemia in rats may render tissues more vulnerable to the inflammatory effects of LPS by enhancing the expression of certain endothelial CAMs.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport 71130-3932, USA.
authors.forename: W H
authors.initials: WH
authors.lastname: Cerwinka
authors.forename: M H
authors.initials: MH
authors.lastname: Cheema
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D019040:E-Selectin / Q000187:drug effects / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D019007:P-Selectin / Q000187:drug effects / Q000378:metabolism; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D008070:Lipopolysaccharides; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol