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Atherosclerotic plaques form when cholesterol, fat and blood cells gradually build up in artery walls, narrowing them and reducing oxygen-rich blood flow from the heart to the body. The Centers for Disease Control and Prevention and the Cleveland Clinic report that one in five U.S. deaths is caused by heart disease, and half of adults ages 45–84 have atherosclerosis without knowing it. High low-density lipoprotein, or LDL, levels raise the risk of atherosclerosis; while apolipoprotein A1, or ApoA1, a major component of high-density lipoprotein, or HDL, protects against it.

Foamy macrophage, often associated with atherosclerotic plaques, with several irregular vacuoles in the cytoplasm surrounded by erythroblasts (arrow).

In a recently published article in the Journal of Lipid Research, Alexander S. Qian and colleagues at McMaster University and Hamilton Health Sciences , a cell-death mediator, in the development of atherosclerotic plaques and necrotic cores. Cholesterol buildup triggers endoplasmic reticulum, or ER, stress in macrophages, which increases Bim expression and leads to macrophage death.

In mice, overexpression of ApoA1 reduces plaque formation. The researchers engineered mice lacking low-density lipoprotein receptors, or LDLR, with or without ApoA1 and fed them a high-fat diet for 10 weeks. Mice lacking both LDLR and ApoA1 developed larger plaques, bigger necrotic cores and higher Bim expression. In bone marrow transplant studies, LDLR- and ApoA1-deficient mice that received Bim-deficient marrow showed reduced plaque and necrotic core size. They also had more circulating immune cells and lower cholesterol and triglyceride levels, regardless of ApoA1 status. The team plans to further study how ApoA1 lowers Bim protein levels in macrophages within plaques.