Nishi Kyoko, Itabe Hiroyuki, Uno Masaaki, Kitazato Keiko T, Horiguchi Hidehisa, Shinno Kiyohito, Nagahiro Shinji
Department of Neurosurgery, School of Medicine, The University of Tokushima, Tokushima, Japan.
Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1649-54. doi: 10.1161/01.atv.0000033829.14012.18.
Oxidation of LDL plays a significant pathogenic role in atherosclerosis. In this study, we attempted to clarify the correlation between the morphology of human atherosclerotic plaques and the oxidized LDL (OxLDL) levels in plasma and carotid plaques.
OxLDL levels (ng/microg apolipoprotein B) in plasma and carotid plaques from 44 patients undergoing carotid endarterectomy and OxLDL levels in 17 control plasma and 9 normal intima samples were determined by a sandwich ELISA by using specific antibodies against OxLDL (DLH3) and apolipoprotein B. The plaques were immunohistochemically classified as macrophage (Mphi)-rich and Mphi-poor. In paired samples from individual patients, plaque OxLDL was nearly 70 times higher than plasma OxLDL (mean+/-SEM, 11.9+/-1.7 vs 0.18+/-0.01 ng/microg apoB, P<0.0001). The OxLDL level was significantly higher in Mphi-rich- than Mphi-poor plaques (19.6+/-2.8 vs 5.50+/-0.77 ng/microg apoB, P<0.0001) and corresponded with DLH3 antigen positivity of the plaques. In patients with Mphi-rich plaques, plasma OxLDL was significantly higher than in the controls (0.20+/-0.02 vs 0.13+/-0.01 ng/microg apoB, P=0.02).
Our results suggest that LDL undergoes further oxidation in plaques, and that high plasma and plaque levels of OxLDL are correlated with the vulnerability to rupture of atherosclerotic lesions.
低密度脂蛋白(LDL)氧化在动脉粥样硬化中起重要致病作用。在本研究中,我们试图阐明人类动脉粥样硬化斑块形态与血浆及颈动脉斑块中氧化型LDL(OxLDL)水平之间的相关性。
采用针对OxLDL(DLH3)和载脂蛋白B的特异性抗体,通过夹心酶联免疫吸附测定法(ELISA)测定了44例行颈动脉内膜切除术患者的血浆和颈动脉斑块中的OxLDL水平(纳克/微克载脂蛋白B),以及17例对照血浆和9例正常内膜样本中的OxLDL水平。对斑块进行免疫组织化学分类,分为富含巨噬细胞(Mphi)型和贫巨噬细胞型。在个体患者的配对样本中,斑块中的OxLDL比血浆中的OxLDL高近70倍(均值±标准误,11.9±1.7 vs 0.18±0.01纳克/微克载脂蛋白B,P<0.0001)。富含Mphi的斑块中的OxLDL水平显著高于贫Mphi的斑块(19.6±2.8 vs 5.50±0.77纳克/微克载脂蛋白B,P<0.0001),且与斑块的DLH3抗原阳性相关。在富含Mphi斑块的患者中,血浆OxLDL显著高于对照组(0.20±0.02 vs 0.13±0.01纳克/微克载脂蛋白B,P=0.02)。
我们的结果表明,LDL在斑块中会进一步氧化,且血浆和斑块中高水平的OxLDL与动脉粥样硬化病变破裂的易感性相关。