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December 19, 1990, Vol 264, No. 23 >
ARTICLE | December 19, 1990

Lipoproteins and Atherogenesis: Title and subTitle BreakCurrent Concepts FREE

Daniel Steinberg, MD, PhD; Joseph L. Witztum, MD
[+] Author Affiliations

Reprint requests to Department of Medicine, University of California—San Diego, La Jolla, CA 92093 (Dr Steinberg).


JAMA. 1990;264(23):3047-3052. doi:10.1001/jama.1990.03450230083034
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Article
References

TODAY there is no longer any doubt about the causative relationship between hypercholesterolemia and premature atherosclerosis. The National Institutes of Health Consensus Conference on Lowering Blood Cholesterol Levels1 and the National Cholesterol Education Program that grew out of it2 were the culmination of many years of experimental and clinical research, including, importantly, a number of positive intervention trials that brought to a close the so-called Cholesterol Controversy,3 ie, the controversy as to the importance of hypercholesterolemia as a causative factor in coronary heart disease. Intensive lipid-lowering regimens have been shown not only to slow the progression of coronary atherosclerosis and reduce the risk of coronary events,4 but even in some cases to lead to absolute regression.5 Best medical practice now calls for appropriate treatment of hypercholesterolemia, and detailed guidelines for treating it are available.2,6

If we are, then, committed in any case to such

REFERENCES

1 +
 NIH Consensus Conference. Lowering blood cholesterol to prevent heart disease . JAMA . 1985;;253:2080-2086.
2 +
 Report on the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults . Arch Intern Med. 1988;;148:36-69.
3 +
Steinberg D.  The cholesterol controversy is over: why did it take so long? Circulation . 1989;;80:1070-1078.
4 +
Tyroler HA.  Lowering plasma cholesterol levels decreases risk of coronary heart disease: an overview of clinical trials . In: Steinberg D, Olefsky JM, eds. Hypercholesterolemia and Atherosclerosis . New York, NY: Churchill Livingstone Inc; 1987;: 99-116.
5 +
Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L.  Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts . JAMA . 1987;;257:3233-3240.
6 +
Witztum JL.  Current approaches to drug therapy for the hypercholesterolemic patient . Circulation . 1989;;80:1101-1114.
7 +
Piper J, Orrild L.  Essential familial hypercholesterolemia and xanthomatosis: follow-up study of twelve Danish families . Am J Med . 1956;;21:34-46.
8 +
Mahley RW.  Development of accelerated atherosclerosis: concepts derived from cell biology and animal model studies . Arch Pathol Lab Med. 1983;;107:393-399.
9 +
Brown MS, Goldstein JL.  A receptor-mediated pathway for cholesterol homeostasis . Science . 1986;;232:34-47.
10 +
Gordon DJ.  HDL and coronary heart disease: a comparison of recent epidemiologic and clinical trial results . In: Miller NE, ed. High Density Lipoproteins and Atherosclerosis II . New York, NY: Elsevier Science Publishing Co Inc; 1989;:3-10.
11 +
Carlson LA, Böttiger LE.  Risk factors for ischemic heart disease in men and women . Acta Med Scand. 1985;;218:207-211.
12 +
Ross R, Glomset JA.  The pathogenesis of atherosclerosis . N Engl J Med. 1976;;295:369-377, 420-425.
13 +
Stemerman MB, Ross R.  Experimental arteriosclerosis, I: fibrous plaque formation in primates, an electron microscopic study . J Exp Med. 1972;;136:769-789.
14 +
Moore S.  Thromboatherosclerosis in normolipemic rabbits: a result of continued endothelial damage . Lab Invest. 1973;;29:478-487.
15 +
Ross R, Glomset J, Kariya B, et al.  A plateletdependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro . Proc Natl Acad Sci USA . 1974;;71:1207-1210.
16 +
Poole JCF, Florey HW.  Changes in the endothelium of the aorta and the behaviour of macrophages in experimental atheroma of rabbits . J Pathol Bacteriol. 1958;;75:245-251.
17 +
Davies PF, Reidy MA, Goode TB, Bowyer DE.  Scanning electron microscopy in the evaluation of endothelial integrity of the fatty lesion in atherosclerosis . Atherosclerosis . 1976;;25:125-130.
18 +
Fowler S, Shio H, Haley NJ.  Characterization of lipid-laden aortic cells from cholesterol-fed rabbits, IV: investigation of macrophage-like properties of aortic cell populations . Lab Invest. 1979;;41:372-378.
19 +
Gerrity RG, Naito HK, Richardson M, Schwartz CJ.  Dietary induced atherogenesis in swine . Am J Pathol. 1979;;95:775-792.
20 +
Aquel NM, Ball RY, Waldman H, Mitchinson MJ.  Monocytic origin of foam cells in human atherosclerotic plaques . Atherosclerosis . 1984;;53: 265-271.
21 +
Steinberg D.  Lipoproteins and atherosclerosis: a look back and a look ahead . Arteriosclerosis . 1983;;3:283-301.
22 +
Ross R.  The pathogenesis of atherosclerosis— an update . N Engl J Med. 1986;;314:488-500.
23 +
Steinberg D.  Metabolism of lipoproteins and their role in the pathogenesis of atherosclerosis . In: Stokes J III, Mancini M, eds. Atherosclerosis Reviews . 1988;;18:1-23.
24 +
Stary HC, Malinow MR.  Ultrastructure of experimental coronary artery atherosclerosis in cynomolgus macaques: a comparison with lesions of other primates . Atherosclerosis. 1982;;43:151-175.
25 +
Stary HC.  Macrophages, macrophage foam cells, and eccentric intimal thickening in the coronary arteries of young children . Atherosclerosis . 1987;;64:91-108.
26 +
McGill HC Jr.  Questions about the natural history of human atherosclerosis . In: Glagov S, Newman WP III, Schaffer S, eds. Pathobiology of the Human Atherosclerotic Plaque . New York, NY: Springer-Verlag NY Inc; 1990;:1-12.
27 +
McGill HC Jr.  Fatty streaks in the coronary arteries and aorta . Lab Invest. 1968;;18:560-564.
28 +
Small DM.  Progression and regression of atherosclerotic lesions: insights from lipid physical biochemistry . Arteriosclerosis . 1988;;8:103-129.
29 +
Gerrity RG.  The role of the monocyte in atherogenesis, I: transition of blood-borne monocytes into foam cells in fatty lesions . Am J Pathol. 1981;;103:181-190.
30 +
Goldstein JL, Ho YK, Basu SK, Brown MS.  Binding site on macrophages that mediates uptake and degradation of acetylated low-density lipoprotein, producing massive cholesterol deposition . Proc Natl Acad Sci U S A . 1979;;76:333-337.
31 +
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL.  Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity . NEngl J Med. 1989;;320:915-924.
32 +
Mahley RW, Innerarity TL, Weisgraber KH, Oh SY.  Altered metabolism (in vivo and vitro) of plasma lipoprotein after selective chemical modification of lysine residues of the apoproteins . J Clin Invest. 1979;;64:743-750.
33 +
Fogelman AM, Schechter JS, Hokom M, Child JS, Edwards PA.  Malondialdehyde alteration of low-density lipoprotein leads to cholesterol accumulation in human monocyte-macrophages . Proc Natl Acad Sci U S A . 1980;;77:2214-2218.
34 +
Henriksen T, Mahoney EM, Steinberg D.  Enhanced macrophage degradation of low-density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low-density lipoproteins . Proc Natl Acad Sci U S A . 1981;;78:6499-6503.
35 +
Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D.  Modification of low-density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low-density lipoprotein phospholipids . Proc Natl Acad Sci U S A . 1984;;81:3883-3887.
36 +
Morel DW, DiCorleto PE, Chisolm GM.  Endothelial and smooth muscle cells alter low-density lipoprotein in vitro by free radical oxidation . Arteriosclerosis . 1984;;4:357-364.
37 +
Henriksen T, Mahoney EM, Steinberg D.  Enhanced macrophage degradation of low-density lipoprotein previously incubated with cultured endothelial cells: recognition by receptor for acetylated low-density lipoproteins . Proc Natl Acad Sci U S A . 1981;;78:6499-6503.
38 +
Heinecke JW, Rosen H, Chait A.  Iron and copper promote modification of low-density lipoprotein by human arterial smooth muscle cells in culture . J Clin Invest. 1987;;74:1890-1894.
39 +
Cathcart MK, Morel DW, Chisolm GM III.  Monocytes and neutrophils oxidize low-density lipoproteins making it cytotoxic . J Leukocyte Biol. 1985;;38:341-350.
40 +
Parthasarathy S, Printz DJ, Boyd D, Joy L, Steinberg D.  Macrophage oxidation of low-density lipoprotein generates a modified form recognized by the scavenger receptor . Arteriosclerosis . 1986;;6:505-510.
41 +
Hiramatsu K, Rosen H, Heinecke JW, Wolfbauer G, Chait A.  Superoxide initiates oxidation of low-density lipoprotein by human monocytes . Arteriosclerosis . 1987;;7:55-60.
42 +
Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M.  Type I macrophage scavenger receptor contains α-helical and collagen-like coiled coils . Nature . 1990;;343:531-535.
43 +
Sparrow CP, Parthasarathy S, Steinberg D.  A macrophage receptor that recognizes oxidized low-density lipoprotein but not acetylated low-density lipoprotein . J Biol Chem. 1989;;264:2599-2604.
44 +
Arai H, Kita T, Yokode M, Narumiya S, Kawai C.  Multiple receptors for modified low-density lipoproteins in mouse peritoneal macrophages: different uptake mechanisms for acetylated and oxidized low-density lipoproteins . Biochem Biophys Res Comm. 1989;;159:1375-1382.
45 +
Palinski W, Rosenfeld ME, Ylä-Herttuala S, et al.  Low-density lipoprotein undergoes oxidative modification in vivo . Proc Natl Acad Sci U S A . 1989;;86:1372-1376.
46 +
Rosenfeld ME, Palinski W, Ylä-Herttuala S, Butler S, Witztum JL.  Distribution of oxidation specific lipid-protein adducts and apolipoprotein B in atherosclerotic lesions of varying severity from WHHL rabbits . Arteriosclerosis . 1989;;10:336-349.
47 +
Ylä-Herttuala S, Palinski W, Rosenfeld ME, et al.  Evidence for the presence of oxidatively modified low-density lipoprotein in atherosclerotic lesions of rabbit and man . J Clin Invest. 1989;;84: 1086-1095.
48 +
Mitchinson MJ, Ball RY, Carpenter KLH, Parums DV.  Macrophages and ceroid in atherosclerosis . In: Suckling KE, Groot PHE, eds. Hyperlipidaemia and Atherosclerosis . London, England: Academic Press; 1988;:117-134.
49 +
Parthasarathy S, Young SG, Witztum JL, Pittman RC, Steinberg D.  Probucol inhibits oxidative modification of low-density lipoprotein . J Clin Invest. 1986;;77:641-644.
50 +
Kita T, Nagano Y, Kokode M, et al.  Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia . Proc Natl Acad Sci U S A . 1987;;84:5928-5931.
51 +
Carew TE, Schwenke DC, Steinberg D.  Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low-density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit . Proc Natl Acad Sci U S A . 1987;;84:7725-7729.
52 +
Quinn MT, Parthasarathy S, Fong LG, Steinberg D.  Oxidatively modified low-density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis . Proc Natl Acad Sci U S A . 1987;;84:2995-2998.
53 +
Quinn MT, Parthasarathy S, Steinberg D.  Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low-density lipoprotein . Proc Natl Acad Sci U S A . 1985;;82:5949-5953.
54 +
Hessler JR, Robertson AL Jr, Chisolm GM.  LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture . Atherosclerosis . 1979;; 32:213-219.
55 +
Henriksen T, Evensen SA, Carlander B.  Injury to human endothelial cells in culture induced by low-density lipoproteins . Scand J Clin Lab Invest. 1979;;39:361-368.
56 +
Cushing SD, Berliner JA, Valente AJ, et al.  Minimally modified low-density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells . Proc Natl Acad Sci U S A . 1990;;87:5134-5138.
57 +
Rajavashisth TB, Andalibi A, Territo MC, et al.  Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins . Nature . 1990;;344:254-257.
58 +
Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD.  Impairment of endotheliumdependent arterial relaxation by lysolecithin in modified low-density lipoproteins . Nature . 1990;; 344:160-162.
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Bevilacqua MP, Pober JS, Wheeler ME, Cotran RS, Gimbrone MA Jr.  Interleukin-1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes and related leukocyte lines . J Clin Invest. 1985;;76:2003-2011.
60 +
Quinn MT, Parthasarathy S, Steinberg D.  Lysophosphatidylcholine: a new chemotactic factor for human monocytes and its potential role in atherogenesis . Proc Natl Acad Sci U S A . 1988;;85:2805-2809.
61 +
Fogelman AM, Haberland ME, Seager J, Hokom M, Edwards PA.  Factors regulating the activities of the low-density lipoprotein receptor and the scavenger receptor on human monocyte-macrophages . J Lipid Res. 1981;;22:1131-1141.
62 +
Steinberg D.  Arterial metabolism of lipoproteins in relation to atherogenesis . In: Lee KT, Onodera K, Tanaka K, eds. Atherosclerosis II: Recent Progress in Atherosclerosis Research. Ann N Y Acad Sci. 1990;;598:125-136.
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Gey KF, Puska P.  Plasma vitamins E and A inversely correlated to mortality from ischemicheart disease in cross-cultural epidemiology . Ann N Y Acad Sci. 1989;;570:268-282.
64 +
Salonen JT.  Selenium in ischaemic heart disease . Int JEpidemiol. 1987;;16:323-328.
65 +
Parthasarathy S, Khoo JC, Miller E, Barnett J, Witztum JL, Steinberg D.  Low-density lipoprotein enriched in oleic acid is protected against oxidative modification: implications for dietary prevention of atherosclerosis . Proc Natl Acad Sci U S A . 1990;; 87:3894-3898.
66 +
Goldstein JL, Ho YK, Brown MS, et al.  Cholesteryl ester accumulation in macrophages resulting from receptor-mediated uptake and degradation of hypercholesterolemic canine beta-very low-density lipoproteins . J Biol Chem. 1980;;255:1839-1848.
67 +
Mahley RW, Innerarity TL, Brown MS.  Cholesteryl ester synthesis in macrophages: stimulation by β-very low-density lipoproteins from cholesterol-fed animals of several species . J Lipid Res. 1980;;21:970-980.
68 +
Koo C, Wernette-Hammond ME, Innerarity TL.  Uptake of canine β-very low-density lipoproteins by mouse peritoneal macrophages is mediated by a low-density lipoprotein receptor . J Biol Chem. 1986;;261:11194-11201.
69 +
Khoo JC, Miller E, McLoughlin P, Steinberg D.  Enhanced macrophage uptake of low-density lipoprotein after self-aggregation . Arteriosclerosis . 1988;;8:348-358.
70 +
Suits AG, Chait A, Aviram M, Heinecke JW.  Phagocytosis of aggregated lipoprotein by macrophages: low-density lipoprotein receptor-dependent foam-cell formation . Proc Natl Acad Sci U S A . 1989;;86:2713-2717.
71 +
Khoo JC, Miller E, McLoughlin P, Steinberg D.  Prevention of low-density lipoprotein aggregation by high density lipoprotein or apolipoprotein A-I . J Lipid Res. 1990;;31:645-652.
72 +
Schwenke DC, Carew TE.  Initiation of atherosclerotic lesions in cholesterol-fed rabbits, II: selective retention of LDL vs selective increases in LDL permeability in susceptible sites of arteries . Arteriosclerosis . 1989;;9:908-918.
73 +
Beaumont JL, Jacotot B, Beaumont V.  L'hyperlipidémie par auto-anticorps: une cause d'athérosclerose . Presse Med. 1967;;75:2315-2320.
74 +
Steinbrecher UP, Fisher M, Witztum JL, Curtiss LK.  Immunogenicity of homologous low-density lipoprotein after methylation, ethylation, acetylation or carbamylation: generation of antibodies specific for derivatized lysine . J Lipid Res. 1984;;25:1109-1116.
75 +
Witztum JL, Steinbrecher UP, Kesaniemi YA, Fisher M.  Autoantibodies to glucosylated proteins in the plasma of patients with diabetes mellitus . Proc Natl Acad Sci U S A . 1984;;81:3204-3208.
76 +
Klimov AN, Denisenko AD, Vinogradov AG, et al.  Accumulation of cholesteryl esters in macrophages incubated with human lipoprotein-antibody autoimmune complex . Atherosclerosis . 1988;;74: 41-46.
77 +
Hansson GK, Jonasson L, Seifert P, Stemme S.  Immune mechanisms in atherosclerosis . Arteriosclerosis . 1989;;9:567-578.
78 +
Geer JC.  Fine structure of human aortic intimal thickening and fatty streaks . Lab Invest . 1965;;14:1764-1783.
79 +
Burk JM, Ross R.  Synthesis of connective tissue macromolecules by smooth muscle . Int Rev Connect Tissue Res. 1979;;8:119-157.
80 +
Gerrity RG.  The role of the monocyte in atherogenesis, II: migration of foam cells from atherosclerotic lesions . Am J Pathol. 1981;;103:191-200.
81 +
Faggiotto A, Ross R.  Studies of hypercholesterolemia in the nonhuman primate, II: fatty streak conversion to fibrous plaque . Arteriosclerosis . 1984;;4:341-356.
82 +
Libby P.  The active roles of cells of the blood vessel wall in health and disease . Molec Aspects Med. 1987;;9:499-567.
83 +
Jonasson L, Holm, J, Skalli O, Bondjers G, Hansson G.  Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque . Arteriosclerosis . 1986;; 6:131-138.
84 +
Masuda J, Ross R.  Atherogenesis during low-level hypercholesterolemia in the nonhuman primate, I: fatty streak formation . Arteriosclerosis . 1990;;10:164-177.
85 +
Masuda J, Ross R.  Atherogenesis during low-level hypercholesterolemia in the nonhuman primate, II: fatty streak conversion to fibrous plaque . Arteriosclerosis . 1990;;10:178-187.
86 +
Ross R, Masuda J, Raines EW, et al.  Localization of PDGF-B protein in macrophages in all phases of atherogenesis . Science . 1990;;248:1009-1012.
87 +
Rubin K, Tingstrom A, Hansson GK, et al.  Induction of β-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions . Lancet . 1988;;1:1353-1356.
88 +
Libby P, Ordovas JM, Auger KR, Robbins AH, Birinyl LK, Dinarello CA.  Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells . Am J Pathol. 1986;;124:179-186.
89 +
Libby P, Ordovas JM, Birinyl LK, Auger KR, Dinarello CA.  Inducible interleukin-1 gene expression in human vascular smooth muscle cells . J Clin Invest. 1986;;78:1432-1438.
90 +
Ylä-Herttuala S, Rosenfeld ME, Parthasarathy S, et al.  Colocalization of 15-lipoxygenase mRNA and protein with epitopes of oxidized low-density lipoprotein in macrophage-rich areas of atherosclerotic lesions . Proc Natl Acad Sci U S A . 1990;;87:6959-6963.
91 +
Ylä-Herttuala S, Rosenfeld ME, Parthasarathy S, et al.  Gene expression in macrophage-rich human atherosclerotic lesions: 15-lipoxygenase and acetyl LDL receptor mRNA colocalize with oxidation specific lipid-protein adducts . J Clin Invest. In press.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
 NIH Consensus Conference. Lowering blood cholesterol to prevent heart disease . JAMA . 1985;;253:2080-2086.
2 +
 Report on the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults . Arch Intern Med. 1988;;148:36-69.
3 +
Steinberg D.  The cholesterol controversy is over: why did it take so long? Circulation . 1989;;80:1070-1078.
4 +
Tyroler HA.  Lowering plasma cholesterol levels decreases risk of coronary heart disease: an overview of clinical trials . In: Steinberg D, Olefsky JM, eds. Hypercholesterolemia and Atherosclerosis . New York, NY: Churchill Livingstone Inc; 1987;: 99-116.
5 +
Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L.  Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts . JAMA . 1987;;257:3233-3240.
6 +
Witztum JL.  Current approaches to drug therapy for the hypercholesterolemic patient . Circulation . 1989;;80:1101-1114.
7 +
Piper J, Orrild L.  Essential familial hypercholesterolemia and xanthomatosis: follow-up study of twelve Danish families . Am J Med . 1956;;21:34-46.
8 +
Mahley RW.  Development of accelerated atherosclerosis: concepts derived from cell biology and animal model studies . Arch Pathol Lab Med. 1983;;107:393-399.
9 +
Brown MS, Goldstein JL.  A receptor-mediated pathway for cholesterol homeostasis . Science . 1986;;232:34-47.
10 +
Gordon DJ.  HDL and coronary heart disease: a comparison of recent epidemiologic and clinical trial results . In: Miller NE, ed. High Density Lipoproteins and Atherosclerosis II . New York, NY: Elsevier Science Publishing Co Inc; 1989;:3-10.
11 +
Carlson LA, Böttiger LE.  Risk factors for ischemic heart disease in men and women . Acta Med Scand. 1985;;218:207-211.
12 +
Ross R, Glomset JA.  The pathogenesis of atherosclerosis . N Engl J Med. 1976;;295:369-377, 420-425.
13 +
Stemerman MB, Ross R.  Experimental arteriosclerosis, I: fibrous plaque formation in primates, an electron microscopic study . J Exp Med. 1972;;136:769-789.
14 +
Moore S.  Thromboatherosclerosis in normolipemic rabbits: a result of continued endothelial damage . Lab Invest. 1973;;29:478-487.
15 +
Ross R, Glomset J, Kariya B, et al.  A plateletdependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro . Proc Natl Acad Sci USA . 1974;;71:1207-1210.
16 +
Poole JCF, Florey HW.  Changes in the endothelium of the aorta and the behaviour of macrophages in experimental atheroma of rabbits . J Pathol Bacteriol. 1958;;75:245-251.
17 +
Davies PF, Reidy MA, Goode TB, Bowyer DE.  Scanning electron microscopy in the evaluation of endothelial integrity of the fatty lesion in atherosclerosis . Atherosclerosis . 1976;;25:125-130.
18 +
Fowler S, Shio H, Haley NJ.  Characterization of lipid-laden aortic cells from cholesterol-fed rabbits, IV: investigation of macrophage-like properties of aortic cell populations . Lab Invest. 1979;;41:372-378.
19 +
Gerrity RG, Naito HK, Richardson M, Schwartz CJ.  Dietary induced atherogenesis in swine . Am J Pathol. 1979;;95:775-792.
20 +
Aquel NM, Ball RY, Waldman H, Mitchinson MJ.  Monocytic origin of foam cells in human atherosclerotic plaques . Atherosclerosis . 1984;;53: 265-271.
21 +
Steinberg D.  Lipoproteins and atherosclerosis: a look back and a look ahead . Arteriosclerosis . 1983;;3:283-301.
22 +
Ross R.  The pathogenesis of atherosclerosis— an update . N Engl J Med. 1986;;314:488-500.
23 +
Steinberg D.  Metabolism of lipoproteins and their role in the pathogenesis of atherosclerosis . In: Stokes J III, Mancini M, eds. Atherosclerosis Reviews . 1988;;18:1-23.
24 +
Stary HC, Malinow MR.  Ultrastructure of experimental coronary artery atherosclerosis in cynomolgus macaques: a comparison with lesions of other primates . Atherosclerosis. 1982;;43:151-175.
25 +
Stary HC.  Macrophages, macrophage foam cells, and eccentric intimal thickening in the coronary arteries of young children . Atherosclerosis . 1987;;64:91-108.
26 +
McGill HC Jr.  Questions about the natural history of human atherosclerosis . In: Glagov S, Newman WP III, Schaffer S, eds. Pathobiology of the Human Atherosclerotic Plaque . New York, NY: Springer-Verlag NY Inc; 1990;:1-12.
27 +
McGill HC Jr.  Fatty streaks in the coronary arteries and aorta . Lab Invest. 1968;;18:560-564.
28 +
Small DM.  Progression and regression of atherosclerotic lesions: insights from lipid physical biochemistry . Arteriosclerosis . 1988;;8:103-129.
29 +
Gerrity RG.  The role of the monocyte in atherogenesis, I: transition of blood-borne monocytes into foam cells in fatty lesions . Am J Pathol. 1981;;103:181-190.
30 +
Goldstein JL, Ho YK, Basu SK, Brown MS.  Binding site on macrophages that mediates uptake and degradation of acetylated low-density lipoprotein, producing massive cholesterol deposition . Proc Natl Acad Sci U S A . 1979;;76:333-337.
31 +
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL.  Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity . NEngl J Med. 1989;;320:915-924.
32 +
Mahley RW, Innerarity TL, Weisgraber KH, Oh SY.  Altered metabolism (in vivo and vitro) of plasma lipoprotein after selective chemical modification of lysine residues of the apoproteins . J Clin Invest. 1979;;64:743-750.
33 +
Fogelman AM, Schechter JS, Hokom M, Child JS, Edwards PA.  Malondialdehyde alteration of low-density lipoprotein leads to cholesterol accumulation in human monocyte-macrophages . Proc Natl Acad Sci U S A . 1980;;77:2214-2218.
34 +
Henriksen T, Mahoney EM, Steinberg D.  Enhanced macrophage degradation of low-density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low-density lipoproteins . Proc Natl Acad Sci U S A . 1981;;78:6499-6503.
35 +
Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D.  Modification of low-density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low-density lipoprotein phospholipids . Proc Natl Acad Sci U S A . 1984;;81:3883-3887.
36 +
Morel DW, DiCorleto PE, Chisolm GM.  Endothelial and smooth muscle cells alter low-density lipoprotein in vitro by free radical oxidation . Arteriosclerosis . 1984;;4:357-364.
37 +
Henriksen T, Mahoney EM, Steinberg D.  Enhanced macrophage degradation of low-density lipoprotein previously incubated with cultured endothelial cells: recognition by receptor for acetylated low-density lipoproteins . Proc Natl Acad Sci U S A . 1981;;78:6499-6503.
38 +
Heinecke JW, Rosen H, Chait A.  Iron and copper promote modification of low-density lipoprotein by human arterial smooth muscle cells in culture . J Clin Invest. 1987;;74:1890-1894.
39 +
Cathcart MK, Morel DW, Chisolm GM III.  Monocytes and neutrophils oxidize low-density lipoproteins making it cytotoxic . J Leukocyte Biol. 1985;;38:341-350.
40 +
Parthasarathy S, Printz DJ, Boyd D, Joy L, Steinberg D.  Macrophage oxidation of low-density lipoprotein generates a modified form recognized by the scavenger receptor . Arteriosclerosis . 1986;;6:505-510.
41 +
Hiramatsu K, Rosen H, Heinecke JW, Wolfbauer G, Chait A.  Superoxide initiates oxidation of low-density lipoprotein by human monocytes . Arteriosclerosis . 1987;;7:55-60.
42 +
Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M.  Type I macrophage scavenger receptor contains α-helical and collagen-like coiled coils . Nature . 1990;;343:531-535.
43 +
Sparrow CP, Parthasarathy S, Steinberg D.  A macrophage receptor that recognizes oxidized low-density lipoprotein but not acetylated low-density lipoprotein . J Biol Chem. 1989;;264:2599-2604.
44 +
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