Cholesterol enrichment of arterial smooth muscle cells upregulates cytokine-induced nitric oxide synthesis.
Cholesterol enrichment of arterial smooth muscle cells upregulates cytokine-induced nitric oxide synthesis.
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动脉平滑肌细胞的胆固醇富集上调细胞因子诱导的一氧化氮合成。
DOI：
10.1006/bbrc.1993.1190
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发表时间：
1993
影响因子：
3.1
通讯作者：
Gross,SS
中科院分区：
文献类型：
--
作者：
Pomerantz,KB;Hajjar,DP;Levi,R;Gross,SS
内皮源性松弛因子/一氧化氮 (EDRF/NO) 由血管壁产生，是血管张力和血压的关键调节剂。 NO 也由血管平滑肌 (VSMC) 产生，可以抑制增殖。由于细胞因子激活的 VSMC 增殖是动脉粥样硬化发展中的一个主要事件，因此我们研究了 VSMC 中胆固醇 (CE) 富集对细胞因子诱导的 NO 合成的影响。用天然 LDL 治疗 VSMC 一周不会促进 CE 积累或改变暴露于内毒素 (LPS) 后的 NO 产生。相比之下，阳离子化 LDL 的 CE 富集将 LPS 诱导的 NO 合成增强了 2-5 倍。虽然 TNF-α 在对照 VSMC 中几乎没有促进 NO 合成，但在 CE 富集后却非常有效。类似地，CE富集增强了IL-1α诱导的NO合成。然而，CE富集并不影响细胞因子与IFN-γ组合协同诱导NO合成。我们的研究结果表明，VSMC 的 CE 富集上调信号转导途径，介导细胞因子和 LPS 诱导 NO 合酶活性。
Endothelium-derived relaxing factor/nitric oxide (EDRF/NO) is produced by the vascular wall and is a key modulator of vascular tone and blood pressure. NO is also produced by vascular smooth muscle (VSMC) where it can inhibit proliferation. Since cytokine-activated VSMC proliferation is a major event in the development of atherosclerosis, we investigated the influence of cholesterol (CE)-enrichment of VSMC on cytokine-induced NO synthesis. Treatment of VSMC with native LDL for one week did not promote CE-accretion or alter NO production following exposure to endotoxin (LPS). In contrast, CE-enrichment by cationized LDL augmented LPS-induction of NO synthesis 2-5-fold. While TNF-α promoted little NO synthesis in control VSMC, it was very potent after CE-enrichment. Similarly, CE-enrichment augmented IL-lα-induced NO synthesis. However, CE-enrichment did not affect the synergistic induction of NO synthesis by cytokines in combination with IFN-γ. Our findings suggest that CE-enrichment of VSMC upregulates signal transduction pathways which mediate cytokine and LPS induction of NO synthase activity.