首页> 美国卫生研究院文献>Journal of Neuropathology and Experimental Neurology >Smooth Muscle Cell Foam Cell Formation Apolipoproteins and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture
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Smooth Muscle Cell Foam Cell Formation Apolipoproteins and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture

机译:平滑肌细胞泡沫细胞形成载脂蛋白和ABCA1在颅内动脉瘤:脂质积累作为动脉瘤壁破裂的促进因素。

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摘要

Saccular intracranial aneurysm (sIA) aneurysm causes intracranial hemorrhages that are associated with high mortality. Lipid accumulation and chronic inflammation occur in the sIA wall. A major mechanism for lipid clearance from arteries is adenosine triphosphate-binding cassette A1 (ABCA1)-mediated lipid efflux from foam cells to apolipoprotein A-I (apoA-I). We investigated the association of wall degeneration, inflammation, and lipid-related parameters in tissue samples of 16 unruptured and 20 ruptured sIAs using histology and immunohistochemistry. Intracellular lipid accumulation was associated with wall remodeling (p = 0.005) and rupture (p = 0.020). Foam cell formation was observed in smooth muscle cells, in addition to CD68- and CD163-positive macrophages. Macrophage infiltration correlated with intracellular lipid accumulation and apolipoproteins, including apoA-I. ApoA-I correlated with markers of lipid accumulation and wall degeneration (p = 0.01). ApoA-I-positive staining colocalized with ABCA1-positive cells particularly in sIAs with high number of smooth muscle cells (p = 0.003); absence of such colocalization was associated with wall degeneration (p = 0.017). Known clinical risk factors for sIA rupture correlated inversely with apoA-I. We conclude that lipid accumulation associates with sIA wall degeneration and risk of rupture, possibly via formation of foam cells and subsequent loss of mural cells. Reduced removal of lipids from the sIA wall via ABCA1-apoA-I pathway may contribute to this process.
机译:囊状颅内动脉瘤(sIA)动脉瘤导致颅内出血,与高死亡率相关。脂质堆积和慢性炎症发生在sIA壁中。从动脉清除脂质的主要机制是三磷酸腺苷结合盒A1(ABCA1)介导的脂质从泡沫细胞向载脂蛋白A-1(apoA-1)流出。我们使用组织学和免疫组织化学方法研究了16例未破裂和20例破裂的sIAs的组织样本中壁变性,炎症和脂质相关参数的关联。细胞内脂质积聚与壁重塑(p = 0.005)和破裂(p = 0.020)有关。除CD68和CD163阳性巨噬细胞外,在平滑肌细胞中也观察到泡沫细胞的形成。巨噬细胞浸润与细胞内脂质蓄积和载脂蛋白(包括apoA-I)相关。 ApoA-I与脂质积累和壁变性的标志物相关(p = 0.01)。 ApoA-I阳性染色与ABCA1阳性细胞共定位,特别是在平滑肌细胞数量多的sIA中(p = 0.003);缺乏这种共定位与壁变性有关(p = 0.017)。已知的sIA破裂的临床危险因素与apoA-I成反比。我们得出的结论是,脂质蓄积与sIA壁变性和破裂风险相关,可能是通过形成泡沫细胞和随后的壁细胞丢失引起的。通过ABCA1-apoA-I途径从sIA壁上去除脂质的减少可能有助于此过程。

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