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Association between 5-lipoxygenase expression and plaque instability in humans
Francesco Cipollone1, Andrea Mezzetti, Maria Luigia Fazia
1Atherosclerosis Prevention Center, G. d'Annunzio University of Chieti, Chieti, Italy. fcipollone@unich.it
Arteriosclerosis, Thrombosis, and Vascular Biology
|June 4, 2005
Summary
Elevated 5-lipoxygenase (5-LO) expression in human carotid plaques correlates with instability and rupture. This suggests 5-LO, via leukotriene B4 (LTB4) and matrix metalloproteinases (MMPs), contributes to atherosclerotic plaque vulnerability.
Area of Science:
- Cardiovascular Biology
- Inflammation Research
- Atherosclerosis Pathogenesis
Background:
- Recent studies suggest 5-lipoxygenase (5-LO) involvement in atherosclerosis development.
- A direct role for 5-LO in modulating human atherosclerotic plaque instability remains uncharacterized.
Purpose of the Study:
- To analyze 5-lipoxygenase (5-LO) expression in human carotid plaques.
- To investigate the mechanism linking 5-LO to plaque instability and rupture.
Main Methods:
- Analysis of 60 human carotid endarterectomy plaques (symptomatic vs. asymptomatic).
- Immunohistochemistry, immunoblotting, densitometry for 5-LO, MMPs, and inflammatory cells.
- Zymography for MMP activity, ELISA for LTB4, and Sirius red for collagen content.
Main Results:
- Symptomatic plaques showed higher macrophage and T-cell infiltration, increased 5-LO, MMP-2, and MMP-9 expression and activity.
- Elevated 5-LO correlated with decreased collagen content and increased LTB4 production.
- 5-LO and MMPs colocalized within activated macrophages in symptomatic plaques.
Conclusions:
- 5-lipoxygenase (5-LO) expression is significantly elevated in symptomatic human carotid plaques.
- Increased 5-LO is associated with acute ischemic syndromes, likely mediated by LTB4 generation, MMP biosynthesis, and subsequent plaque rupture.