Published Online
on March 20, 2008

A more recent version of this article appeared on May 1, 2008

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Submitted on August 28, 2007
Accepted on September 24, 2007

Enhanced Expression of Lp-PLA₂ and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaques

Dallit Mannheim MD; Joerg Herrmann MD; Daniele Versari MD; Mario Gössl MD; Fredric B. Meyer MD; Joseph P. McConnell PhD; Lilach O. Lerman MD, PhD; and Amir Lerman MD^*

From the Divisions of Cardiovascular Diseases (D.M., J.H., D.V., M.G., L.O.L., A.L.), Neurosurgery (F.B.M.), Cardiovascular-Laboratory Medicine and Immunochemical Core Laboratory (J.P.M.), and Nephrology and Hypertension (L.O.L.), Mayo Clinic College of Medicine, Rochester, Minn.

^* To whom correspondence should be addressed. E-mail: lerman.amir{at}mayo.edu.

Background and Purpose—Circulating lipoprotein-associated phospholipase A₂ (Lp-PLA₂) has emerged as a novel biomarker for cardiovascular diseases. However, the correlation between the plaque expression of Lp-PLA₂ and plaque oxidative stress, inflammation, and stability as well as the clinical presentation remains poorly defined, especially for cerebrovascular disease. Therefore, this study was performed to test the hypothesis that Lp-PLA₂ expression is higher in symptomatic than in asymptomatic carotid plaques of patients undergoing carotid endarterectomy.

Methods—The expression of Lp-PLA₂ in 167 carotid artery plaques was determined by immunoblotting and immunostaining. Plaque oxidative stress, inflammation, and stability were quantified by NAD(P)H oxidase p67phox and MMP-2 immunoblotting, oxidized LDL (oxLDL) immunoreactivity, macrophage and Sirius red collagen staining. Lysophosphatidylcholine 16:0 (lysoPC) concentration was measured in 55 plaques using liquid chromatography tandem mass spectrometry.

Results—Lp-PLA₂ expression was significantly higher in plaques of symptomatic patients than asymptomatic patients (1.66±0.19 versus 1.14±0.10, P<0.05) and localized mainly to shoulder and necrotic lipid core areas in colocalization with oxLDL and macrophage content. Similarly, Lp-PLA₂ expression was related to collagen content, which was lower in plaques from symptomatic patients than in plaques from asymptomatic patients (9.1±2.2 versus 18.5±1.7% of staining/field, P<0.001). LysoPC plaque concentration was significantly higher in plaques of symptomatic than asymptomatic patients (437.0±57.91 versus 228.84±37.00 mmol/L, P<0.05).

Conclusions—Symptomatic carotid artery plaques are characterized by increased levels of Lp-PLA₂ and its product lysoPC in correlation with markers of tissue oxidative stress, inflammation, and instability. These findings strongly support a role for Lp-PLA2 in the pathophysiology and clinical presentation of cerebrovascular disease.

Key words: Lp-PLA_2, lysophosphatidylcholine • carotid • atherosclerosis • unstable plaque

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