Signal Transduction in Atherosclerosis: Second Messengers and Regulation of Cellular Cholesterol Trafficking

  • Kenneth B. Pomerantz
  • Andrew C. Nicholson
  • David P. Hajjar
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 369)


While the anatomic pathology of atherosclerotic plaque development is well understood, the cellular mechanisms which contribute to lesion progression remain undefined. Prior to the 1970’s, the prevailing view of atherogenesis was the concept that lipid infiltration from plasma-derived LDL was necessary and sufficient to elicit an atherogenic response. However, a fresh and intriguing view was proposed by Ross and Glomset in 1976. They suggested that atherogenesis was a consequence of the cellular response to injury (Ross and Glomset, 1976), and that humoral and cell-derived mediators, such as platelet-derived growth factor (PDGF) played a role in atherogenesis by promoting arterial smooth muscle cell hyperplasia (Ross et al., 1974). These seminal studies formed the basis for a novel approach to the study of atherosclerosis which was based on the concept that atherosclerosis may be viewed as a chronic inflammatory response to high concentrations of native or modified low density lipoprotein (LDL), which in turn elicits a series of cellular and biochemical events which result in alterations in endothelial cell phenotype, macrophage infiltration, smooth muscle cell migration, proliferation, foam cell development, and matrix deposition (Ross, 1986). Implicit in the Ross hypothesis is the concept that mediators released by cells comprising the lesion contribute to its development. Endothelial cells, macrophages, and arterial smooth muscle cells are all sources of, and targets for, a variety of humoral- and cell-derived mediators which are known to modulate cholesterol metabolism. In this review, we address the hypothesis that soluble mediators (growth factors and cytokines), derived from vascular and inflammatory cells, directly influence processes controlling cholesterol metabolism through the generation of second messengers including eicosanoids and cyclic nucleotides. We also discuss the possibility that derangements in intracellular cholesterol trafficking within smooth muscle cell and/or macrophage-derived foam cells, may be a result of disruption of the cytokine/eicosanoid network.


Smooth Muscle Cell Cholesteryl Ester High Density Lipoprotein Scavenger Receptor Arterial 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.


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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Kenneth B. Pomerantz
    • 1
  • Andrew C. Nicholson
    • 2
  • David P. Hajjar
    • 3
  1. 1.Department of MedicineCornell University Medical CollegeNew YorkUSA
  2. 2.Department of PathologyCornell University Medical CollegeNew YorkUSA
  3. 3.Department of BiochemistryCornell University Medical CollegeNew YorkUSA

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