Mannheim Dallit, Herrmann Joerg, Versari Daniele, Gössl Mario, Meyer Fredric B, McConnell Joseph P, Lerman Lilach O, Lerman Amir
Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Stroke. 2008 May;39(5):1448-55. doi: 10.1161/STROKEAHA.107.503193. Epub 2008 Mar 20.
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.
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.
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).
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.
循环脂蛋白相关磷脂酶A2（Lp-PLA2）已成为心血管疾病的一种新型生物标志物。然而，Lp-PLA2在斑块中的表达与斑块氧化应激、炎症、稳定性以及临床表现之间的相关性仍不明确，尤其是在脑血管疾病方面。因此，本研究旨在验证以下假设：在接受颈动脉内膜切除术的患者中，有症状的颈动脉斑块中Lp-PLA2的表达高于无症状斑块。
通过免疫印迹和免疫染色测定167个颈动脉斑块中Lp-PLA2的表达。通过NAD(P)H氧化酶p67phox和MMP-2免疫印迹、氧化低密度脂蛋白（oxLDL）免疫反应性、巨噬细胞和天狼星红胶原染色对斑块氧化应激、炎症和稳定性进行定量分析。使用液相色谱串联质谱法测量55个斑块中溶血磷脂酰胆碱16:0（lysoPC）的浓度。
有症状患者斑块中Lp-PLA2的表达明显高于无症状患者（1.66±0.19对1.14±0.10，P<0.05），且主要定位于肩部和坏死脂质核心区域，与oxLDL和巨噬细胞含量共定位。同样，Lp-PLA2的表达与胶原含量相关，有症状患者斑块中的胶原含量低于无症状患者斑块中的胶原含量（9.1±2.2对18.5±1.7%染色/视野，P<0.001）。有症状患者斑块中lysoPC的浓度明显高于无症状患者（437.0±57.91对228.84±37.00 mmol/L，P<0.05）。
有症状的颈动脉斑块的特征是Lp-PLA2及其产物lysoPC水平升高，与组织氧化应激、炎症和不稳定性标志物相关。这些发现有力地支持了Lp-PLA2在脑血管疾病病理生理学和临床表现中的作用。
