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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2459.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Macrophage Cholesterol Metabolism, Apolipoprotein E, and Scavenger Receptor AI/II mRNA in Atherosclerosis-Susceptible and -Resistant Mice

Gideon Friedman; Arie Ben-Yehuda; Yedida Dabach; Gideon Hollander; Sharona Babaey; Mazal Ben-Naim; Olga Stein; Yechezkiel Stein

From the Division of Medicine, Geriatric Unit (G.F., A.B.-Y., S.B.); the Lipid Research Laboratory, Division of Medicine, Hadassah University Hospital (Y.D., G.H., Y.S.); and the Department of Experimental Medicine, Hebrew University-Hadassah Medical School (M.B.-N., O.S.), Jerusalem, Israel.

Correspondence to Prof Y. Stein, Lipid Research Laboratory, Division of Medicine, Hadassah University Hospital, PO Box 12220, Jerusalem 91120, Israel. E-mail ystein{at}hadassah.org.il

Abstract—Female mice known to be susceptible (C57BL) and resistant (C3H and BALB/c) to diet-induced atherosclerosis were studied. Feeding of a cholate-containing atherogenic diet for 1 month resulted in an increase in plasma total cholesterol, little or no change in total phospholipids and high density lipoprotein (HDL) cholesterol, and a fall in HDL phospholipid, which was most pronounced in the C57BL strain. In elicited macrophages, cholesterol esterification was lower with acetylated low density lipoprotein (acLDL) and higher with ß-very low density lipoprotein (ß-VLDL) in C57BL than in C3H or BALB/C strains. In resident macrophages, acLDL enhanced cholesterol esterification more than did rabbit ß-VLDL. With acLDL, more apolipoprotein E (apoE) was recovered in all macrophage cultures. In macrophages from chow-fed mice, most apoE was in the medium, whereas in mice fed an atherogenic diet, half of the apoE was in the cells. ApoE protein was highest in macrophages from BALB/c mice fed an atherogenic diet; an increase in apoE mRNA occurred in BALB/c and C3H macrophages. Scavenger receptor AI/II mRNA was significantly higher in macrophages from atherosclerosis-resistant mice. Thus, higher HDL phospholipid and plasma apoE levels (reported by others), together with high macrophage scavenger receptor AI/II mRNA, could inhibit accretion of cholesterol in the vessel wall in the 2 resistant strains.

Key Words: macrophages • cholesteryl ester • apolipoprotein E • scavenger receptors • atherosclerosis

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