Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells
Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells
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DOI：
10.1007/s11010-006-9280-x
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发表时间：
2007-01-01
影响因子：
4.3
通讯作者：
Douglas, Stephen A.
中科院分区：
文献类型：
--
作者：
Aiyar, Nambi;Disa, Jyoti;Douglas, Stephen A.
溶血磷脂酰胆碱（LPC）是氧化LDL的主要生物活性脂质成分，被认为是炎症细胞和内皮细胞中氧化LDL的许多炎症作用的原因。炎症诱导的血管平滑肌细胞从收缩表型向增殖/分泌表型的转变是动脉粥样硬化特征的血管重塑的标志；然而，LPC在这一过程中的作用尚未得到充分描述。本研究验证了LPC是冠状动脉平滑肌细胞（CASMCs）炎症刺激的假设。在培养的人CASMCs中，LPC刺激花生四烯酸的时间和浓度依赖性释放，花生四烯酸对磷脂酶A(2)和C抑制敏感。LPC刺激花生四烯酸代谢产物白三烯- b -4和6-酮前列腺素F-1 α在同一时间内释放。LPC还被发现刺激碱性成纤维细胞生长因子的释放，以及刺激细胞因子GM-CSF、IL-6和IL-8的释放。棕榈酸取代的LPC对这些信号的刺激效果最佳。刺激花生四烯酸、炎症细胞因子和生长因子释放，表明LPC可能通过影响炎症过程在动脉粥样硬化的进展中发挥多因素作用。
Lysophosphatidylcholine (LPC) is the major bioactive lipid component of oxidized LDL, thought to be responsible for many of the inflammatory effects of oxidized LDL described in both inflammatory and endothelial cells. Inflammation-induced transformation of vascular smooth muscle cells from a contractile phenotype to a proliferative/secretory phenotype is a hallmark of the vascular remodeling that is characteristic of atherogenesis; however, the role of LPC in this process has not been fully described. The present study tested the hypothesis that LPC is an inflammatory stimulus in coronary artery smooth muscle cells (CASMCs). In cultured human CASMCs, LPC stimulated time- and concentration-dependent release of arachidonic acid that was sensitive to phospholipase A(2) and C inhibition. LPC stimulated the release of arachidonic acid metabolites leukotriene-B-4 and 6-keto-prostaglandin F-1 alpha, within the same time course. LPC was also found to stimulate basic fibroblast growth factor release as well as stimulating the release of the cytokines GM-CSF, IL-6, and IL-8. Optimal stimulation of these signals was obtained via palmitic acid-substituted LPC species. Stimulation of arachidonic acid, inflammatory cytokines and growth factor release, implies that LPC might play a multifactorial role in the progression of atherosclerosis, by affecting inflammatory processes.