Macrophage cholesterol metabolism, apolipoprotein E, and scavenger receptor AI/II mRNA in atherosclerosis-susceptible and -resistant mice

Female mice known to be susceptible (C57BL) and resistant (C3H and BALB/c) to diet-induced atherosclerosis were studied. Feeding of a cholate-containi ng atherogenic diet for 1 month resulted in an increase in plasma total cho lesterol, little or no change in total phospholipids and high density lipop rotein (HDL) cholesterol, and a fall in HDL phospholipid, which was most pr onounced in the C57BL strain. In elicited macrophages, cholesterol esterifi cation was lower with acetylated low density lipoprotein (acLDL) and higher with beta -very low density lipoprotein (beta -VLDL) in C57BL than in C3H or BALB/C strains. In resident macrophages, acLDL enhanced cholesterol este rification more than did rabbit beta -VLDL. With acLDL, more apolipoprotein E (apoE) was recovered in all macrophage cultures. In macrophages from cho w-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 macro phages from BALB/c mice fed an atherogenic diet; an increase in apoE mRNA o ccurred in BALB/c and C3H macrophages. Scavenger receptor AI/II mRNA was si gnificantly higher in macrophages from atherosclerosis-resistant mice. Thus , higher HDL phospholipid and plasma apoE levels (reported by others), toge ther with high macrophage scavenger receptor AI/II mRNA, could inhibit accr etion of cholesterol in the vessel wall in the 2 resistant strains.