Beta-migrating very low-density lipoprotein conjugates with acrolein in high-cholesterol diet-fed rabbits and localizes to atherosclerotic lesions with macrophages

Protein-conjugated acrolein (PC-Acro) is detected in atherosclerotic lesions, and we demonstrated previously that acrolein-conjugated low-density lipoproteins induce macrophage foam cell formation. Although it has been suggested that β-migrating very low-density lipoprotein (βVLDL) is taken up by macrophages during atherogenesis, the modification of βVLDL with acrolein and its localization on lesions are still unclear. The purpose of this study was to clarify the localization of PC-Acro in atherosclerotic lesions and to determine the role of acrolein-conjugated βVLDL in atherogenesis. Male New Zealand white rabbits were fed 0.5% cholesterol-containing rabbit chow for 8 weeks, and used as an animal model of atherosclerosis. PC-Acro and malondialdehyde (MDA)-conjugated protein levels, which has been used widely as a means to detect oxidized low-density lipoprotein (LDL), in plasma were increased in the 0.5% cholesterol-containing diet-induced animal model of atherosclerosis, whereas their level was unchanged in the control diet fed rabbit. PC-Acro was detected in βVLDL by western blot analysis, and acrolein-conjugated βVLDL was effectively taken up by THP-1 macrophages. By immunohistochemical analysis, PC-Acro and macrophages were detected at the internal elastic lamina of the aorta, which was the initial lesion of atherosclerosis. These results suggest that acrolein-conjugated βVLDL has an important role in the initiation of atherosclerosis via the induction of macrophage foam cell formation in the atherosclerotic lesion.