Role of Macrophages in Atherogenesis

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1. To investigate the role of macrophages and lymphocytes in human atherosclerosis, immunohistological methods combined with electron microscopic analysis were used to assess the cellular infiltrates in human arterial intima such as normal areas on gross inspection, fatty streaks and atheromatous plaques. In the lesions of fatty streaks and atheromatous plaques including the fibrous cap and shoulder region, OKM1+ LeuM3+ macrophages as well as macrrophage foam cells were intimately coexisted with OKT3+ lymphocytes. It was worthy to note that such colocalization of macrophages and T lymphocytes was detectable in some areas of grossly normal intima. Electron microscopy demonstrated the direct cellular contact not only between lymphocytes and macrophages but also among lymphocyte-lymphocyte and macrophage-macrophage.2. To assess the development and initial lesion sites of cerebral atherosclerosis in rabbits, the dorsal surface of the cerebral artery segment covering from the vertebral arteries to posterior cerebral arteries was thoroughly examined by scanning microscopy. The results showed that hypertension coupled with hypercholesterolemia induced atherosclerosis in certain vulnerable regions of the cerebral arteries.3. Interaction of macrophages with cultured endothelila cells was studied. Pretreatment with LDL and VLDL increased adhesion of macrophages to endothelial cells. Macrophages from hypercholesterolemic animals showed enhanced attachment to the endothelila cells; they moved more quickly when examined by time-lapse cinephotomicrography.4. We produced an in vitro model of a blood vessel wall consisting of human umbilical vein endothelial cells cultured on human amnion.