Apolipoprotein B accumulation and development of foam cell lesions in coronary arteries of hypercholesterolemic swine.
We wished to determine whether plasma low density lipoproteins (LDL) preferentially accumulate at specific anatomical sites in swine coronary arteries that are predisposed to atherosclerotic lesion development, and if so, to determine what alteration in wall structure may be responsible for this accumulation. Therefore, we measured the accumulation of apolipoprotein B (apo B), the major protein in LDL, by electroimmunoassay in seven separate segments of coronary arteries from swine fed a hypercholesterolemic or normolipemic control diet for periods of 4 to 15 weeks. Apo B accumulation was greater in segments from swine fed a hypercholesterolemic diet than in segments for corresponding time intervals from swine fed a normolipemic diet and was greater in proximal than in distal segments (nonbranch points) of coronary arteries. This accumulation of apo B generally increased with time on the hypercholesterolemic diet, already appearing elevated relative to controls at 4 weeks on the hypercholesterolemic diet, whereas the initial appearance of foam cells in these regions occurred at 6 weeks. Apo B was localized by immunofluorescence almost exclusively to areas of diffuse intimal thickening in the proximal portions of the coronary arteries and to focal areas of intimal thickening or cushions at branch points in more distal segments. In these regions, apo B was found primarily in edematous, cell-sparse zones close to the lumen surface, rather than the smooth muscle cell-rich areas making up most of the thickened intima. Apo B in these areas was associated with Alcian blue-positive areas suggested to contain sulfated glycosaminoglycans, which may be responsible for the preferential LDL accumulation. The diffuse and focal intimal thickening does not appear to have been induced by the hypercholesterolemia or the subsequent deposition of LDL, since such thickening was found at the same sites and to about the same degree in the normolipemic control animals. Thus, this study has shown that the areas of earliest and preferential accumulation of LDL are sites of intimal thickening containing deposits of sulfated glycosaminoglycan, and that these are the regions at which the first foam cell lesions eventually appear. These findings add additional strong circumstantial data linking LDL deposition in arteries to the atherosclerotic process.
D000818:Animals; D001053:Apolipoproteins / Q000097:blood / Q000378:metabolism*; D001055:Apolipoproteins B; D002791:Cholesterol, Dietary / Q000494:pharmacology; D003327:Coronary Disease / Q000097:blood / Q000209:etiology* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D005487:Foam Cells / Q000473:pathology; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism*; D007122:Immunoelectrophoresis / Q000379:methods; D008297:Male; D013552:Swine; D013997:Time Factors
D001053:Apolipoproteins; D001055:Apolipoproteins B; D002791:Cholesterol, Dietary