Immunohistochemical Localization of Lipoprotein Lipase and Apolipoprotein E in Human Atherosclerotic Lesions.

Abstract

Lipoprotein lipase (LPL) and apolipoprotein E (apo E) are both involved in the metabolism of triglyceride-rich lipoproteins. In the arterial wall, these two proteins may be associated with foam cell formation during atherogenesis, yet their localization and cellular sources in the arterial intima are not fully defined. To evaluate the potential roles of these two proteins in various stages of human atherosclerosis, we studied the distribution of LPL and apo E in diffuse intimal thickening, fatty streaks and fibrous plaques of aorta and coronary artery using specific antibodies against human LPL and apo E. In aorta with diffuse intimal thickening, LPL was found in both intimal and medial smooth muscle cells whereas apo E was present only in the intima and was mainly associated with the surrounding extracellular matrix. In fatty streaks and fibrous plaques, LPL and apo E were widely distributed, and were either cell-associated or bound to the extracellular matrix. Double immunohistochemical staining using LPL/apo E and macrophage-specific antibodies revealed that LPL or apo E was colocalized with macrophage-derived foamy and nonfoamy cells. Furthermore, LPL and apo E were variably associated with the extracellular matrix in these areas. As the lesions advanced, LPL was diffusely stained in macrophages and smooth muscle cells in the proximity of the lipid core and fibrous cap, whereas apo E was associated with macrophages around the lipid core. These immunohistochemical findings suggest that LPL can be produced by a variety of cellular sources in the arterial wall, including smooth muscle cells and macrophages, while apo E is mainly derived from macrophages. We speculate that LPL secretion and apo E secretion from macrophages in atherosclerotic lesions are regulated differently and their respective functions in foam cell formation during atherogenesis merit further investigation.