A modern view of atherogenesis

Colin J. Schwartz, Anthony J. Valente, Eugene A. Sprague

Research output: Contribution to journalComment/debate

148 Scopus citations

Abstract

Two key events in the atherogenic cascade are the focal influx and accumulation of low-density lipoprotein (LDL) cholesterol at arterial sites having a predilection for atherosclerotic lesion development and the recruitment of blood monocytes to these lesion-prone sites. Both processes are enhanced in the setting of hyperlipidemia and dyslipoproteinemia. The monocytes recruited to the endothelial surface subsequently migrate to the subendothelial space under the directed guidance of chemoattractants, such as monocyte chemotactic protein-1 and oxidatively modified LDL. These cells then undergo activation-differentiation to become macrophages. At the same time, LDL, and probably other lipoproteins such as the small dense LDL particles and lipoprotein (a), traverse the endothelium and undergo oxidative modification by reactive oxygen species. These oxidatively modified lipoproteins are recognizable by the non-down-regulating macrophage scavenger receptor. Their uptake by these receptors results in the formation of the foam cell characteristic of early-stage atherosclerosis. As monocyte recruitment and lipoprotein influx continue, the lesion grows and develops into the fatty streak. Subsequent foam cell necrosis due to the influence of cytotoxic oxidatively modified LDL and increased collagen synthesis by intimal smooth muscle cells lead to the established atherosclerotic lesion referred to as the fibrous plaque. As our understanding of the mechanisms involved in the pathogenesis of atherosclerosis has evolved over the past few years, novel strategies for intervention in the atherogenic process have emerged.

Original languageEnglish (US)
Pages (from-to)B9-B14
JournalThe American journal of cardiology
Volume71
Issue number6
DOIs
Publication statusPublished - Feb 25 1993

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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Schwartz, C. J., Valente, A. J., & Sprague, E. A. (1993). A modern view of atherogenesis. The American journal of cardiology, 71(6), B9-B14. https://doi.org/10.1016/0002-9149(93)90139-4