Lipoprotein modification and macrophage uptake: Role of pathologic cholesterol transport in atherogenesis

Yury I. Miller, Soo Ho Choi, Longhou Fang, Sotirios Tsimikas

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Low-density lipoprotein (LDL) is a major extracellular carrier of cholesterol and, as such, plays important physiologic roles in cellular function and regulation of metabolic pathways. However, under pathologic conditions of hyperlipidemia, oxidative stress and/or genetic disorders, specific components of LDL become oxidized or otherwise modified, and the transport of cholesterol by modified LDL is diverted from its physiologic targets toward excessive cholesterol accumulation in macrophages and the formation of macrophage “foam” cells in the vascular wall. This pathologic deposition of modified lipoproteins and the attendant pro-inflammatory reactions in the artery wall lead to the development of atherosclerotic lesions. Continued accumulation of immunogenic modified lipoproteins and a pro-inflammatory milieu result in the progression of atherosclerotic lesions, which may obstruct the arterial lumen and/or eventually rupture and thrombose, causing myocardial infarction or stroke. In this review, we survey mechanisms of LDL modification and macrophage lipoprotein uptake, including results of recent in vivo experiments, and discuss unresolved problems and controversial issues in this growing field. Future directions in studying foam cell formation may include introducing novel animal models, such as hypercholesterolemic zebrafish, enabling dynamic in vivo observation of macrophage lipid uptake.

Original languageEnglish (US)
Pages (from-to)229-251
Number of pages23
JournalSub-Cellular Biochemistry
Volume51
DOIs
StatePublished - 2010

Keywords

  • Atheroscleosis
  • Cholesterol transport
  • Foam cell
  • Low density lipoprotein
  • Macrophage

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology
  • Cancer Research

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