The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life

Abstract

We have studied the cell and matrix composition of normal intima and of atherosclerotic lesions in the coronary arteries of 691 subjects less than 40 years old. These arteries were obtained at autopsy and fixed by perfusion with glutaraldehyde under physiological pressure. A defined segment of the left coronary artery, known for its susceptibility to develop advanced lesions, was studied by light and electron microscopy. The initial intimal lesion occurred in infants and consisted in an increase in intimal macrophages and presence of isolated lipid-laden macrophages (foam cells). At puberty, more substantial accumulations of foam cells, accompanied now by lipid droplets in smooth muscle cells and by thinly scattered extracellular lipid (fatty streaks), were present. After puberty, an increasing number of subjects had intermediate lesions and atheroma. Intermediate lesions, characterized by greatly increased extracellular lipid, were the link between fatty streaks and atheroma. Atheroma was characterized by a massive core of extracellular lipid that damaged arterial structure by displacing normal intimal cells and matrix. In the third and more often in the fourth decade, some atheroma contained greatly increased collagen and smooth muscle cells above the lipid core (fibroatheroma). Collagenization and thickening were more marked when evidence of thrombotic deposits was present on the surface or within lesions. Smooth muscle cells were present in the intima of all subjects from birth. In early lesions, lipid in the intima was not associated with an increase in the number of smooth muscle cells. Smooth muscle cells were increased in lesions containing massive extracellular lipid, more so in those having, in addition, a thrombotic component; smooth muscle cells with massive basement membranes occurred in advanced lesions. Macrophages and macrophage foam cells were the cells that increased intimal cellularity at the onset of lesions. Other cell types associated with lesions were lymphocytes, mast cells, and plasma cells, but all of these were less numerous than either smooth muscle cells or macrophages. From birth, intima was always thicker opposite the flow divider wall of a bifurcation (eccentric thickening). When atherosclerotic lesions of any type were present in coronary arteries, the amount of lipid and accompanying cell reactions were greatest in eccentric thickening; intermediate lesions and atheroma were present only in eccentric thickening while fibroatheroma often extended beyond eccentric thickening.