Lipoproteins, Macrophages and Atherosclerosis

  • Daniel Steinberg
Conference paper
Part of the Veröffentlichungen aus der Geomedizinischen Forschungsstelle der Heidelberger Akademie der Wissenschaften book series (HD AKAD, volume 1987/88 / 1987/4)


The fatty streak, the earliest recognized gross lesion in the atherogenic process, is characterized by an accumulation of lipid-laden “foam cells”. Recent studies have established that this lesion can -- and usually does -- develop beneath an intact endothelium. Furthermore, it has been shown that most of these cells are derived from circulating monocytes that enter the arterial wall and take up residence there as tissue macrophages. Some of these cells are derived from medial smooth muscle cells, particularly in later lesions, but the majority are macrophages. Early attempts to convert macrophages to foam cells by incubation in the presence of high concentrations of LDL were unsuccessful and this was traced to the rather low number of receptors for native LDL they express. Studies by Goldstein, Brown and coworkers established that the macrophage expresses a unique receptor that can take up chemically acetylated LDL at a sufficiently high rate to generate foam cells in culture. However, there was no evidence that chemical acetylation occurs to any significant extent in vivo. Thus, there remained an unresolved paradox regarding the mechanism of foam cell formation and thus the initiation of the fatty streak.


Foam Cell Foam Cell Formation Fatty Streak Intact Endothelium Medial Smooth Muscle Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Gerrity RG (1981) The role of the monocyte in atherogenesis. II. Migration of foam cells from atheroslerotic lesions. Am J Pathol 103: 191–200PubMedGoogle Scholar
  2. Gerrity RG, Goss JA, Soby L (1985) Control of monocyte recruitment by chemotactic factor(s) in lesion-prone areas of swine aorta. Arteriosclerosis 5: 55–66.PubMedCrossRefGoogle Scholar
  3. Goldstein JL, Ho YK, Basu SK, Brown MS (1979) Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci USA 76: 333–337PubMedCrossRefGoogle Scholar
  4. Henriksen T, Mahoney EM, Steinberg D (1981) Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: Recognition by the receptor for acetylated low density lipoproteins. Proc Natl Acad Sci USA 78: 6499–6503Google Scholar
  5. Henriksen T, Mahoney EM, Steinberg D (1983) Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis 3: 149–159PubMedCrossRefGoogle Scholar
  6. Morel DW, Hessler JR, Chisolm GM (1983) Low density lipoprotein cytotoxicity induced by free radical pewroxidation of lipid. J Lipid Res 24: 1070–1076PubMedGoogle Scholar
  7. Parthasarathy S, Steinbrecher UP, Barnett J, Witztum JL, Steinberg D (1985) Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci USA 82: 3000–3004.PubMedCrossRefGoogle Scholar
  8. Parthasarathy S, Fong LG, Otero D, Steinberg D (1986) Recognition of resolubilized apoproteins from delipidated, oxidatively-modified low density lipoprotein (LDL) by the acetyl-LDL receptor. Proc Natl Acad Sci USA (in press)Google Scholar
  9. Quinn MT, Parthasarathy S, Steinberg D (1986) Oxidized low density lipoprotein is chemotactic for human monocytes. Circulation 74: II-378 (abstr.)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • Daniel Steinberg
    • 1
  1. 1.Specialized Center of Research on Arteriosclerosis University of CaliforniaSan Diego, La JollaUSA

Personalised recommendations