open access

Vol 15, No 1 (2009)
Review papers
Published online: 2009-02-24
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Patophysiology of atherosclerosis based on research on apoE-knockout mice and their usefulness in checking new antiatherosclerotic agents

Jacek Jawień, Marek Jawień
Acta Angiologica 2009;15(1):1-9.

open access

Vol 15, No 1 (2009)
Review papers
Published online: 2009-02-24

Abstract

Although atherosclerosis was previously thought to be primarily a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. This review describes the history of the new atherogenetic concept, including the pivotal role of apoE-knockout mice in understanding the inflammatory background of atherosclerosis.
The pivotal stage of atherogenesis is antigen presentation by macrophages to T lymphocytes. This antigen could be a fragment of oxidized LDL"digested" by macrophage, heat shock protein 60, β2 glycoprotein I, or fragments of bacterial antigens. During interaction between these cells, an immunological response of type T helper 1 (cellular) or T helper 2 (humoral) arises. Th1 response and its mediators: (IFN-γ, TNF-α, interleukin 1, interleukin 12, and interleukin 18) increase atherogenesis, whereas Th2 response and its mediators: (interleukin 4, interleukin 5, and interleukin 10) decrease the development of atherosclerosis. The concept of atherosclerosis as an inflammatory disease is quite fresh; however, it is already considered an undisputable achievement of science, bringing particular therapeutic consequences.
Since inflammation plays an important role in atherogenesis, during recent years it has become apparent that the 5-lipoxygenase (5-LO) pathway may play an important role in modifying the pathogenesis of atherosclerosis. These data raised the possibility that antileukotriene drugs may be an effective treatment regimen in atherosclerosis. In fact, we have found that among apoE and LDLR-double knockout mice the inhibition of FLAP, as well as cysteinyl leukotriene receptor blockade, was able to significantly prevent the development of atherosclerosis in gene-targeted mice.

Abstract

Although atherosclerosis was previously thought to be primarily a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. This review describes the history of the new atherogenetic concept, including the pivotal role of apoE-knockout mice in understanding the inflammatory background of atherosclerosis.
The pivotal stage of atherogenesis is antigen presentation by macrophages to T lymphocytes. This antigen could be a fragment of oxidized LDL"digested" by macrophage, heat shock protein 60, β2 glycoprotein I, or fragments of bacterial antigens. During interaction between these cells, an immunological response of type T helper 1 (cellular) or T helper 2 (humoral) arises. Th1 response and its mediators: (IFN-γ, TNF-α, interleukin 1, interleukin 12, and interleukin 18) increase atherogenesis, whereas Th2 response and its mediators: (interleukin 4, interleukin 5, and interleukin 10) decrease the development of atherosclerosis. The concept of atherosclerosis as an inflammatory disease is quite fresh; however, it is already considered an undisputable achievement of science, bringing particular therapeutic consequences.
Since inflammation plays an important role in atherogenesis, during recent years it has become apparent that the 5-lipoxygenase (5-LO) pathway may play an important role in modifying the pathogenesis of atherosclerosis. These data raised the possibility that antileukotriene drugs may be an effective treatment regimen in atherosclerosis. In fact, we have found that among apoE and LDLR-double knockout mice the inhibition of FLAP, as well as cysteinyl leukotriene receptor blockade, was able to significantly prevent the development of atherosclerosis in gene-targeted mice.
Get Citation

Keywords

atherosclerosis; gene-targeting; apoE-knockout mice; leukotrienes

About this article
Title

Patophysiology of atherosclerosis based on research on apoE-knockout mice and their usefulness in checking new antiatherosclerotic agents

Journal

Acta Angiologica

Issue

Vol 15, No 1 (2009)

Pages

1-9

Published online

2009-02-24

Bibliographic record

Acta Angiologica 2009;15(1):1-9.

Keywords

atherosclerosis
gene-targeting
apoE-knockout mice
leukotrienes

Authors

Jacek Jawień
Marek Jawień

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