Dietary cholesterol-induced changes in macrophage characteristics. Relationship to atherosclerosis.
In diet-induced hypercholesterolemia, circulating monocytes adhere to the endothelium of the vessel wall and emigrate into the intima. Atherosclerotic lesions may develop, characterized by the presence of lipid-laden macrophages and proliferating smooth muscle cells recruited from the media. Using rat peritoneal macrophages, the authors examined the influence of diet-induced hypercholesterolemia on several variables of macrophage function that may contribute to lesion formation, including adhesion to bovine aortic endothelial cells (BAECs) and vascular smooth muscle cells (VSMCs), the production of chemoattractants and mitogens for VSMCs, and the release of the reactive oxygen species, superoxide. In general, a hypercholesterolemia-induced augmentation of macrophage function was observed. In comparison with macrophages from normal animals (N M phi s), macrophages from hypercholesterolemic animals (H M phi s) were 50-80% more adhesive to BAECs and VSMCs. H M phi-secreted products increased VSMC migration 6 to 7-fold, whereas N M0s only stimulated motility 2.5-fold. In addition, H M phi-conditioned media produced increased VSMC growth 5-fold, compared with a 2.5-fold increase produced by N M phi-conditioned media. Although the production of superoxide was found to be the same for both N M phi s and H M phi s, the release of superoxide by macrophages found in the intima of hypercholesterolemic animals may contribute to the necrosis of cells in the developing lesion. These results suggest that dietary cholesterol may accelerate atherosclerotic lesion formation by inducing specific changes in the properties of circulating monocytes and intimal macrophages.
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology*; D001202:Ascitic Fluid / Q000166:cytology; D002448:Cell Adhesion; D002633:Chemotaxis; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004036:Diet, Atherogenic; D006937:Hypercholesterolemia / Q000150:complications; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism
D002791:Cholesterol, Dietary; D013481:Superoxides; D002784:Cholesterol