Adipophilin expression is increased in symptomatic carotid atherosclerosis -: Correlation with red blood cells and cholesterol crystals
Adipophilin expression is increased in symptomatic carotid atherosclerosis -: Correlation with red blood cells and cholesterol crystals
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DOI：
10.1161/strokeaha.106.478867
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发表时间：
2007-06-01
期刊：
影响因子：
8.3
通讯作者：
Lindsberg, Perttu J.
中科院分区：
文献类型：
--
作者：
Nuotio, Krista;Isoviita, Pia M.;Lindsberg, Perttu J.
背景和目的-Adipophilin 是一种在含脂细胞中表达的脂肪分化相关蛋白。通过 DNA 微阵列分析，我们之前发现亲脂蛋白基因 (ADFP) 在有症状的颈动脉斑块 (CP) 中过度表达。这促使我们进一步研究脂肪亲和素在颈动脉粥样硬化中相对于症状状态的作用。方法-在颈动脉内膜切除术中获得了九十八个高级别（> 70%）CP。通过定量实时RT-PCR测量ADFP mRNA的相对表达量，并通过Western blotting定量脂肪亲和蛋白的相对量。通过免疫组织化学获得了与外渗红细胞和细胞外胆固醇晶体的详细拓扑相关性。 结果 - 与无症状 CP 相比，有症状的 CP 中 ADFP mRNA 的相对表达在 mRNA 水平（1.82 +/- 0.19[SE] 与 1.25 +/- 0.15，P + 0.012）和蛋白质水平（1.04 +/- 0.012）上均有所增加。 0.23 与 0.46 +/- 0.14，P = 0.043）。 Adipophilin 与巨噬细胞泡沫细胞、渗出的红细胞 (P < 0.0001) 和胆固醇晶体 (P < 0.0001) 共定位，其表达与 CP 宏观溃疡相关 (P < 0.0001)。结论 - 斑块内出血可能导致细胞内脂质积累和随后的 adipophilin 表达。由于脂肪亲和素会阻止胆固醇从载脂细胞中流出，因此它们可能会死亡并形成坏死的脂质核心，从而破坏斑块的稳定性。
Background and Purpose - Adipophilin is an adipose differentiation - related protein expressed in lipid- containing cells. Using DNA microarray analysis, we previously found the adipophilin gene ( ADFP) to be overexpressed in symptomatic carotid plaques ( CP). This led us to further examine the role of adipophilin in carotid atherosclerosis relative to symptom status.Methods - Ninety- eight high- grade ( > 70%) CPs were obtained in carotid endarterectomy. The relative expression of ADFP mRNA was measured by quantitative real- time RT- PCR, and the relative amount of adipophilin protein was quantified with Western blotting. Detailed topographical correlations with extravasated red blood cells and extracellular cholesterol crystals were obtained by means of immunohistochemistry.Results - The relative expression of ADFP mRNA was increased in symptomatic compared with asymptomatic CPs at both the mRNA level ( 1.82 +/- 0.19[ SE] versus 1.25 +/- 0.15, P + 0.012) and the protein level ( 1.04 +/- 0.23 versus 0.46 +/- 0.14, P = 0.043). Adipophilin colocalized with macrophage foam cells, extravasated red blood cells ( P < 0.0001), and cholesterol crystals ( P < 0.0001), and its expression associated with macroscopic ulceration of CP ( P < 0.0001).Conclusions - Intraplaque hemorrhages may contribute to intracellular lipid accumulation and consequent adipophilin expression. Because adipophilin blocks cholesterol efflux from lipid- laden cells, they may die and develop a necrotic lipid core, thereby destabilizing the plaque.