APOPTOTIC CELL-DEATH IN ATHEROSCLEROTIC PLAQUES OF HYPERLIPIDEMIC KNOCKOUT MICE

In an attempt to understand the roles of apoptosis in the development of atherosclerosis, we classified lesions developed in the aortas of a po E-and LDL receptor-deficient mice, murine models of atherosclerosis , and determined frequency, spatial distribution and cell types of apo ptotic cells in each lesion. Terminal deoxynucleotidyl transferase-med iated dUTP nick end labeling (TUNEL) and nuclear staining with propidi um iodide were used to demonstrate apoptotic cells. Mean frequencies o f TUNEL-positive cells were as follows: 0% in Type I: 0.3% in Type II, 0.05% in Type III, 0.06% in Type IV and 0.06% in Type V lesions. Most of the TUNEL-positive cells were filled with fat and distributed in c lose proximity to lipid pools. The TUNEL-positive cells in the intimal side of the lipid cores were macrophages, while some of those in the adventitial side were smooth muscle cells. In conclusion, apoptosis is involved in the active turn-over of foam cells of both macrophage-and smooth muscle cell-lineage especially in the early atherosclerotic le sions of the hyperlipidemic mice. (C) 1997 Elsevier Science Ireland Lt d.