High-density lipoproteins retard the progression of atherosclerosis and favorably remodel lesions without suppressing indices of inflammation or oxidation.
OBJECTIVE
Protective properties of high-density lipoproteins (HDL) may include reverse cholesterol transport and suppression of oxidation and inflammation. These were investigated in vivo, as were the effects of HDL on the characteristics of atherosclerotic lesions.


RESULTS
Male apolipoprotein E knockout (apoE-/-) and apoE-/- mice expressing human apolipoprotein AI (hAI/apoE-/-) were studied up to 20 weeks after commencing a high-fat diet. Plasma HDL cholesterol was twice as high in hAI/apoE-/- mice. Over time, aortic root lesion area remained less in hAI/apoE-/- mice, although plaques became complex. In advanced lesions, plaque lipid was higher in apoE-/- mice, whereas plaque collagen and alpha actin were increased in hAI/apoE-/- mice. In nonlesional aorta, mRNA abundance for pro-inflammatory proteins (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule-1 [ICAM-1], monocyte chemoattractant protein-1 [MCP-1]) increased between 4 and 16 weeks in apoE-/- (but not wild-type) mice, and were not reduced by elevated HDL. Autoantibodies to malondialdehyde low-density lipoprotein (LDL) increased progressively in apoE-/- mice, with similar results in hAI/apoE-/- mice.


CONCLUSIONS
HDL retarded plaque size progression despite greatly elevated plasma cholesterol. This effect was over a wide range of lesion severity. Expression of hAI reduced plaque lipid and increased the proportion of plaque occupied by collagen and smooth muscle cells, but did not affect indicators of inflammation or LDL oxidation.
Department of Medicine, Marc and Ruti Bell Program in Vascular Biology in the Leon H. Charney Division of Cardiology, and Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
Robin P
RP
Choudhury
James X
JX
Rong
Eugene
E
Trogan
Valerie I
VI
Elmalem
Hayes M
HM
Dansky
Jan L
JL
Breslow
Joseph L
JL
Witztum
John T
JT
Fallon
Edward A
EA
Fisher
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000097:blood; D001057:Apolipoproteins E; D001161:Arteriosclerosis / Q000517:prevention & control*; D001323:Autoantibodies; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D001323:Autoantibodies; D018932:Chemokine CCL2; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D002784:Cholesterol