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Oxidized Phospholipids as Mediators of Vascular Disease

  • Chapter
Oxidative Stress and Vascular Disease

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 224))

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Abstract

Atherosclerosis has been thought to be an inevitable consequence of aging, but progress in understanding the molecular and pathological basis of this vascular disease through the work of Brown and Goldstein (1) has made it clear that this need not be the case. Specific risk factors for this disease exist, and these elucidate general mechanisms underlying this disease. For example, failure to adequately remove plasma cholesterol in the form of low-density lipoprotein (LDL) from the bloodstream, due to mutations in the LDL receptor, leads to high concentration of plasma LDL that is sufficient to cause the disease. Other work (2) demonstrated that LDL underwent oxidative modification to generate particles that were more effective in causing pathological effects. Elevated levels of LDL promoted this pathologic change. Ross proposed a “response-to-injury” model of atherosclerosis (3), where damage to the vessel wall initiated the disease. A refined version of this model recognizes that the early steps in atherogenesis need not necessarily be initiated by the cytotoxicity of oxidized LDL, but rather by activation of an inflammatory response in vascular tissue. Oxidation inappropriately stimulates the normal inflammatory response of endothelial cells and leukocytes. Activation of this normally tightly regulated inflammatory response program, by factors which themselves are not well regulated, (i.e. oxidation of LDL by uncontrolled chemical reactions) leads to chronic, unregulated inflammation of the vascular wall. Such a chronic inflammatory process remodels the vessel wall, drives plaque formation, and destabilizes plaque structures, all key events in atherosclerosis.

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Authors
  1. Sean Davies
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  2. Thomas McIntyre
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  3. Stephen Prescott
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  4. Guy Zimmerman
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  1. Boston University School of Medicine, Boston, MA, USA

    John F. Keaney Jr. M.D. (Associate Professor of Medicine and Pharmacology) (Associate Professor of Medicine and Pharmacology)

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Davies, S., McIntyre, T., Prescott, S., Zimmerman, G. (2000). Oxidized Phospholipids as Mediators of Vascular Disease. In: Keaney, J.F. (eds) Oxidative Stress and Vascular Disease. Developments in Cardiovascular Medicine, vol 224. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4649-8_6

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