Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture.
Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture.
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DOI：
10.1016/j.atherosclerosis.2012.09.037
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发表时间：
2013-01
期刊：
影响因子：
5.3
通讯作者：
Keavney B
中科院分区：
文献类型：
--
作者：
Lee K;Santibanez-Koref M;Polvikoski T;Birchall D;Mendelow AD;Keavney B
常驻巨噬细胞在动脉粥样斑块破裂中发挥重要作用。由于斑块中复杂的细胞异质性，与斑块破裂相关的巨噬细胞基因表达特征尚未完全确定。我们的目的是表征破裂和稳定的人类动脉粥样硬化病变中常驻斑块巨噬细胞的差异基因表达。我们对稳定和破裂的人类动脉粥样硬化斑块中分离的富含巨噬细胞的区域进行了全基因组表达分析。使用临床、放射学和组织病理学标准将颈动脉内膜切除术标本中存在的斑块指定为稳定或破裂。通过激光显微切割从 5 个破裂斑块和 6 个稳定斑块中切除富含巨噬细胞的区域。使用 Affymetrix 微阵列进行转录谱分析。这些图谱是活化巨噬细胞的特征。在 10% 的错误发现率下，稳定斑块和破裂斑块之间有 914 个基因存在差异表达。这些发现在 14 个进一步稳定和破裂的样本中得到了证实，其中 11 个基因的子集具有最高的表达差异 (p < 0.05)。通路分析显示，与稳定斑块相比，破裂斑块中 PPAR/脂肪细胞因子信号通路的成分上调最显着 (p = 5.4 × 10−7)。该通路的两个关键成分脂肪酸结合蛋白 4 (FABP4) 和瘦素在破裂斑块的巨噬细胞中的表达量分别高出九倍 (p = 0.0086) 和五倍 (p = 0.0012)。我们发现从稳定和破裂的人类动脉粥样斑块中分离的巨噬细胞之间的基因表达特征存在差异。我们的研究结果表明 FABP4 和瘦素参与动脉粥样硬化和斑块破裂的进展，并表明斑块内 PPAR/脂肪细胞因子信号传导的下调可能具有治疗潜力。 ► 我们检查了稳定斑块和破裂斑块中巨噬细胞的基因表达。 ► PPAR/脂肪细胞因子信号通路在破裂斑块中上调。 ► FABP4和瘦素在破裂的动脉粥样斑块巨噬细胞中高表达。 ► PPAR/脂肪细胞因子信号传导的下调可能具有治疗潜力。
Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences (p < 0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques (p = 5.4 × 10−7). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold (p = 0.0086) and five-fold (p = 0.0012) greater expression respectively in macrophages from ruptured plaques. We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential. ► We examined gene expression in macrophages from stable and ruptured plaques. ► The PPAR/adipocytokine signaling pathway was upregulated in ruptured plaques. ► FABP4 and Leptin were highly expressed in ruptured atheromatous plaque macrophages. ► Down-regulation of PPAR/adipocytokine signaling may have therapeutic potential.
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影响因子：
82.9
作者：
Erbay, Ebru;Babaev, Vladimir R.;Mayers, Jared R.;Makowski, Liza;Charles, Khanichi N.;Snitow, Melinda E.;Fazio, Sergio;Wiest, Michelle M.;Watkins, Steven M.;Linton, MacRae F.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.
影响因子：
39.3
作者：
Peeters, Wouter;de Kleijn, Dominique P. V.;Pasterkamp, Gerard
通讯作者：
Pasterkamp, Gerard
影响因子：
5.3
作者：
Di Taranto, Maria Donata;Morgante, Alberto;Salvatore, Francesco
通讯作者：
Salvatore, Francesco
DOI：
10.1161/atvbaha.109.190314
发表时间：
2009-08-01
影响因子：
8.7
作者：
Ionita, Mihaela G.;Vink, Aryan;de Kleijn, Dominique P. V.
通讯作者：
de Kleijn, Dominique P. V.
影响因子：
4.4
作者：
Liu, Hongtao;Shi, Bo;Pope, Richard M.
通讯作者：
Pope, Richard M.