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 diminishes fatty streak lesion formation. To examine the mechanism, prelesional events in atherosclerotic plaque development were examined in 6- to 8-week-old apo E-deficient and apo E-deficient/human apo A-I transgenic mice. A quantitative assessment of subendothelial lipid deposition by freeze-fracture and deep-etch electron microscopy indicated that elevated apo A-I did not affect the distribution or amount of aortic arch subendothelial lipid deposits. Immunohistochemical staining for VCAM-1 demonstrated similar expression on endothelial cells at prelesional aortic branch sites from both apo E-deficient and apo E-deficient/human apo A-I transgenic mice. Transmission electron microscopy revealed monocytes bound to the aortic arch in mice of both genotypes, and immunohistochemical staining demonstrated that the area occupied by bound mononuclear cells was unchanged. Serum paraoxonase and aryl esterase activity did not differ between apo E-deficient and apo E-deficient/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/human apo A-I transgenic mice at a stage following lipid deposition, endothelial activation, and monocyte adherence, without increases in HDL-associated paraoxonase.
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, New York 10021, USA.
H M
HM
Dansky
S A
SA
Charlton
C B
CB
Barlow
M
M
Tamminen
J D
JD
Smith
J S
JS
Frank
J L
JL
Breslow
D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000473:pathology; D016632:Apolipoprotein A-I / Q000502:physiology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D043303:Aryldialkylphosphatase; D018845:CD11 Antigens / Q000032:analysis; D002448:Cell Adhesion; D008076:Cholesterol, HDL / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D004950:Esterases / Q000097:blood; D005487:Foam Cells / Q000473:pathology*; D005613:Freeze Etching; D005614:Freeze Fracturing; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000032:analysis; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009000:Monocytes / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D018845:CD11 Antigens; D008076:Cholesterol, HDL; D008055:Lipids; D019010:Vascular Cell Adhesion Molecule-1; D004950:Esterases; D043303:Aryldialkylphosphatase