کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5947918 1172375 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture
ترجمه فارسی عنوان
افزایش بیان پروتئین 4 اتصال دهنده اسید چرب و لپتین در ماکروفاژهای ساکنین، پراکندگی پلاک آترواسکلروز را مشخص می کند
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
چکیده انگلیسی

ObjectiveResident 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.Methods and resultsWe 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.ConclusionsWe 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 226, Issue 1, January 2013, Pages 74-81
نویسندگان
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