Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis
Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis
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DOI：
10.1111/j.1365-2796.2010.02304.x
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发表时间：
2011-02-01
影响因子：
11.1
通讯作者：
Paulsson-Berne, G.
中科院分区：
文献类型：
--
作者：
Agardh, H. E.;Folkersen, L.;Paulsson-Berne, G.
Agardh HE, Folkersen L, Ekstrand J, Marcus D, Swedenborg J, Hedin U, Gabrielsen A, Paulsson-Berne G（瑞典斯德哥尔摩卡罗林斯卡医学院心血管实验研究医学系；瑞典斯德哥尔摩卡罗林斯卡医学院分子医学与外科学系）。脂肪酸结合蛋白4/aP2的表达与颈动脉粥样硬化斑块不稳定相关。实习医学杂志2011；269: 200 - 210. -目标。动脉粥样硬化斑块易损的分子基础与斑块破裂和血栓栓塞的高风险是复杂的。我们研究了斑块稳定性的临床评估是否与病变内差异表达的mRNA转录物相关。方法与结果。前瞻性收集有症状和无症状颈动脉狭窄手术患者的动脉内膜切除术样本，并将临床参数记录在卡罗林斯卡颈动脉内膜切除术生物库中。mRNA表达谱（n = 40）和定量RT-PCR （n = 105）显示，与无症状患者相比，近期出现斑块不稳定症状的患者的病变中脂肪酸结合蛋白4 （FABP4/aP2）水平升高（阵列：FC = 2, P < 0.05; RT-PCR: P < 0.05）。在mRNA水平上，FABP4/aP2与单核/巨噬细胞谱系的细胞标记CD36、CD68和CD163以及cd4阳性T细胞相关。FABP4/aP2 mRNA的表达也与白三烯途径、5-脂氧合酶和白三烯A4水解酶相关。此外，转录谱分析发现CD52和亲脂蛋白是与FABP4/aP2相关性最高的mrna。免疫组化证实，巨噬细胞和T细胞分别表达FABP4/aP2和FABP4/aP2。结论：FABP4/aP2 mRNA水平在不稳定颈动脉斑块中表达升高。免疫组化分析显示FABP4/aP2定位于巨噬细胞群体。这些FABP4/ ap2阳性巨噬细胞是一种重要且普遍的表型，可能在清除介导的脂质摄取和斑块细胞代谢应激之间提供新的联系。此外，FABP4/aP2与炎症和斑块不稳定的其他重要信号相关，如T细胞和白三烯酶。综上所述，这些结果表明FABP4/aP2是连接血管和细胞脂质积累与炎症的关键因素。
Agardh HE, Folkersen L, Ekstrand J, Marcus D, Swedenborg J, Hedin U, Gabrielsen A, Paulsson-Berne G (Department of Medicine, Experimental Cardiovascular Research, Karolinska Institutet; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden). Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis. J Intern Med 2011; 269: 200-210.Objective.The molecular basis for atherosclerotic plaque vulnerability with high risk of plaque rupture and thromboembolism is complex. We investigated whether clinical estimates of plaque stability correlate with differentially expressed mRNA transcripts within the lesion.Methods and results.Endarterectomy samples from patients undergoing surgery for symptomatic and asymptomatic carotid stenosis were prospectively collected and clinical parameters recorded in the Biobank of Karolinska Carotid Endarterectomies. mRNA expression profiling (n = 40) and quantitative RT-PCR (n = 105) revealed increased levels of fatty acid-binding protein 4 (FABP4/aP2) in lesions from patients with recent symptoms of plaque instability compared to asymptomatic patients (array: FC = 2, P < 0.05; RT-PCR: P < 0.05). At the mRNA level, FABP4/aP2 correlated with the cell markers CD36, CD68 and CD163 of monocyte/macrophage lineage as well as with CD4-positive T cells. FABP4/aP2 mRNA expression was also correlated with enzymes of the leukotriene pathway, 5-lipoxygenase and leukotriene A4 hydrolase. In addition, analysis of transcript profiles identified CD52 and adipophilin as the mRNAs with the highest correlation with FABP4/aP2. Expression of FABP4/aP2 by macrophages and CD52 by T cells in the lesion was confirmed by immunohistochemistry.Conclusions.Expression of FABP4/aP2 is increased at the mRNA level in unstable carotid plaques. Immunohistochemical analyses showed localization of FABP4/aP2 to macrophage populations. These FABP4/aP2-positive macrophages constitute an important and prevalent phenotype and could provide a new link between scavenging-mediated lipid uptake and cellular metabolic stress in plaque. In addition FABP4/aP2 correlates with other important signs of inflammation and plaque instability, such as T cells and leukotriene enzymes. Taken together, these results indicate that FABP4/aP2 is a key factor connecting vascular and cellular lipid accumulation to inflammation.