Monocyte/macrophage accumulation and smooth muscle cell phenotypes in early atherosclerotic lesions of human aorta

Abstract

In a search for early atherosclerotic lesions, we have investigated grossly normal areas of human thoracic aortas taken at autopsy from 40 trauma victims aged from 3 to 40 years. Two areas of aorta were compared: lesion predisposed to atherosclerosis (LP) area localized on the dorsal aspect of the vessel along the row of intercostal branching sites, and lesion resistant (LR) area located on the ventral aspect of the vessel. Accumulation of apolipoprotein B (apo B) was found in LP aortic area of each child older than 6 years. Similar retention of apo B in LR area appeared only in aortas of teenagers. The apo B staining increased with age in both areas tested but was usually of a greater extent in LP area than in LR area. Typical smooth muscle cells (SMCs) and a few monocytes/macrophages (Mn/Mph) were revealed in the intimal layer of all aortas examined. The number of Mn/Mph dramatically increased in LP areas of individuals over 17 years. Quantitative study of double stained sections has shown a 2- to 6-fold enhanced number of Mn/Mph in LP area compared with LR aortic area of 10 men over 21 years. Focal infiltration of Mn/Mph in aortas of young adults occurred without endothelial denudation. In addition, some intimal SMCs in LP area of 12 aortas out of 29 expressed desmin and contained well-developed endoplasmic reticulum, while such cells were seldom detected in LP area of the vessels. Thus, focal accumulation of apo B with subsequent Mn/Mph infiltration and SMC phenotypic modulation in LP aortic area of young adults may be causally involved in fatty streak and atherosclerotic plaque formation.