Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation
Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation
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DOI：
10.1194/jlr.m032862
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发表时间：
2013-05-01
影响因子：
6.5
通讯作者：
Bot, Ilze
中科院分区：
文献类型：
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作者：
Bot, Martine;de Jager, Saskia C. A.;Bot, Ilze
溶血磷脂酸（LPA）是一种生物活性的溶血磷脂，在动脉粥样硬化斑块中积累。它具有激活肥大细胞的能力，这可能会加剧斑块的进展。在这项研究中，我们的目的是研究LPA是否通过调节肥大细胞功能来促进斑块的不稳定。我们在这里通过成像质谱方法显示，几种LPA物种存在于动脉粥样硬化斑块中。随后，我们证明LPA是一种有效的肥大细胞激活剂，与其他触发器不同，它有利于胰蛋白酶的释放。在动脉粥样硬化的颈动脉段局部给予LPA可增加血管周围肥大细胞的激活状态，促进斑块内出血和巨噬细胞募集，但不影响斑块细胞凋亡。肥大细胞稳定剂色莫利可预防lpa介导的肥大细胞活化引起的斑块内出血。最后，肥大细胞参与了这些事件，在肥大细胞缺陷的动物中，血管周围LPA的作用缺乏进一步强调。我们证明斑块中LPA积累的增加诱导血管周围肥大细胞激活，并以这种方式促进斑块在体内的不稳定。本研究指出，局部LPA可用性是影响动脉粥样硬化斑块稳定性的重要因素。-博特，M， S. C. A.德雅格，L.麦卡莱斯，H. M.拉格劳，T. J. C.范伯克，P. H. A.奎克斯，J.柯伊伯，R. M. A.希林，E. A. L.比森，和I.博特。溶血磷脂酸通过增加血管炎症触发肥大细胞驱动的动脉粥样硬化斑块不稳定。[j] .油脂杂志。2013。54: 1265 - 1274。
Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.-Bot, M., S. C. A. de Jager, L. MacAleese, H. M. Lagraauw, T. J. C. van Berkel, P. H. A. Quax, J. Kuiper, R. M. A. Heeren, E. A. L. Biessen, and I. Bot. Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation. J. Lipid Res. 2013. 54: 1265-1274.