RISK OF THROMBOSIS IN HUMAN ATHEROSCLEROTIC PLAQUES - ROLE OF EXTRACELLULAR LIPID, MACROPHAGE, AND SMOOTH-MUSCLE CELL CONTENT

Objective-To assess the size of the lipid pool and the number of smoot h muscle cells and monocyte/macrophages in human aortic plaques that w ere intact and to compare the results with those in aortic plaques und ergoing ulceration and thrombosis. Design-The lipid pool was measured as a percentage of the total cross sectional area of the plaque. Immun ohistochemistry was used to identify cell types (monocytes/macrophages (Mphi) by EBM11 and HAM56, smooth muscle cells by alpha actin). The a rea of the tissue occupied by each cell type was measured by quantitat ive microscopy in the peripheral (shoulder) area of the plaque and the plaque cap. Absolute counts of each cell type were expressed as the r atio of SMC:Mphi. Material-Aortas were obtained at necropsy from men a ged less than 69 years who died suddenly (within 6 hours of the onset of symptoms) of ischaemic heart disease. 155 plaques from 13 aortas we re studied. Four aortas showed intact plaques only (group A, n = 31). Nine aortas showed both intact plaques (group B, n = 79) and plaques t hat were undergoing thrombosis (group C, n = 45). Results-In 41 (91.1% ) of the 45 plaques undergoing thrombosis (group C) lipid pools occupi ed more than 40% of the cross sectional area of the plaque. Only 12 (1 0.9%) of the 110 intact plaques (groups A + B) had lipid pools of this size. The mean size of the lipid pool in plaques of groups A, B, and C was 12.7%, 27.3% and 56.7% respectively. Compared with intact plaque s those undergoing thrombosis contained a smaller volume of smooth mus cle cells (2.8% v 11.8%) and a larger volume of monocyte/macrophages ( 13.7% v 2.9%) in the plaque cap. The ratio of the number of smooth mus cle cells to monocytes/macrophages was 7.8 in group A plaques, 4.1 in group B plaques, and 1-0 in group C plaques. This gradient was the res ult of an absolute increase in monocyte/macrophages and an absolute de crease in smooth muscle cells. Conclusions-In the aorta ulceration and thrombosis were characteristic of plaques with a high proportion of t heir volume occupied by extracellular lipid, and in which there was a shift toward a preponderance of monocyte/macrophages compared with smo oth muscle cells in the cap.