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. 2008 May;39(5):1448-55.
doi: 10.1161/STROKEAHA.107.503193. Epub 2008 Mar 20.

Enhanced expression of Lp-PLA2 and lysophosphatidylcholine in symptomatic carotid atherosclerotic plaques

Dallit Mannheim  1 , Joerg Herrmann, Daniele Versari, Mario Gössl, Fredric B Meyer, Joseph P McConnell, Lilach O Lerman, Amir Lerman
Affiliations

Enhanced expression of Lp-PLA2 and lysophosphatidylcholine in symptomatic carotid atherosclerotic plaques

Dallit Mannheim et al. Stroke. 2008 May.

Abstract

Background and purpose: Circulating lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has emerged as a novel biomarker for cardiovascular diseases. However, the correlation between the plaque expression of Lp-PLA(2) 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-PLA(2) expression is higher in symptomatic than in asymptomatic carotid plaques of patients undergoing carotid endarterectomy.

Methods: The expression of Lp-PLA(2) 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-PLA(2) 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-PLA(2) 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-PLA(2) 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.

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Figures

Figure 1
Figure 1
Expression of Lp-PLA2, NAD(P)H oxidase p67phox, and MMP-2 in carotid artery plaque of asymptomatic and symptomatic patients with a differential expression pattern in TIA and stroke patients (top panel: representative blots; bottom panel: quantitative results; *P<0.05 vs asymptomatic, †P<0.05 vs TIA).
Figure 2
Figure 2
Representative immunostaining for Lp-PLA2 (positive brown staining) showing expression in the core and shoulder area; insets show high magnification of the necrotic core and shoulder. Original magnification × 10, inset ×25.
Figure 3
Figure 3
Immunofluorescence of a carotid artery plaque shoulder region showing colocalization (yellow) of Lp-PLA2 (red) and ox-LDL (green; panel A&B) and with lox-1 (green; panel C&D). The same area is characterized by colocalization (yellow) of macrophages (red) and oxLDL (green; panel E&F).
Figure 4
Figure 4
Concentration of lysoPC in carotid plaques of asymptomatic, TIA, and stroke patients showing an increased lysoPC content in plaques of symptomatic patients with a differential expression pattern in TIA and stroke patients. *P<0.05 vs asymptomatic.
Figure 5
Figure 5
Concentration of macrophages and collagen in carotid plaques of asymptomatic, TIA, and stroke patients showing an increased macrophage and a decreased collagen content in symptomatic patients, again with a differential pattern in TIA and stroke patients. *P<0.05 vs asymptomatic.
See this image and copyright information in PMC

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