Apo A-I inhibits foam cell formation in apo E-deficient mice after monocyte adherence to endothelium

We have previously shown that expression of the human apo A-I transgene on the apo E-deficient background increases HDL cholesterol and greatly dimini shes fatty streak lesion formation. To examine the mechanism, prelesional e vents in atherosclerotic plaque development were examined in 6- to 8-week-o ld apo E-deficient and apo E-deficient/human apo A-I transgenic mice. A qua ntitative assessment of subendothelial lipid deposition by freeze-fracture and deep-etch electron microscopy indicated that elevated apo A-I did not a ffect the distribution or amount of aortic arch subendothelial lipid deposi ts. Immunohistochemical staining for VCAM-1 demonstrated similar expression on endothelial cells at prelesional aortic branch sites from both apo E-de ficient and apo E-deficient/human apo A-I transgenic mice. Transmission ele ctron microscopy revealed monocytes bound to the aortic arch in mice of bot h genotypes, and immunohistochemical staining demonstrated that the area oc cupied by bound mononuclear cells was unchanged. Serum paraoxonase and aryl esterase activity did not differ between apo E-deficient and apo E-deficie nt/human apo A-I transgenic mice. These data suggest that increases in apo A-I and HDL cholesterol inhibit foam cell formation in apo E-deficient/huma n apo A-I transgenic mice at a stage following Lipid deposition, endothelia l activation, and monocyte adherence, without increases in HDL-associated p araoxonase.