Arsonists and firefighters: the perpetual inflammatory civil war for survival.
Arsonists and firefighters: the perpetual inflammatory civil war for survival.
复制标题
纵火犯和消防员：为了生存而进行的永恒的煽动性内战。
DOI：
10.1161/circulationaha.114.010006
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发表时间：
2014
期刊：
影响因子：
37.8
通讯作者：
Karliner,JoelS
中科院分区：
文献类型：
--
作者：
Karliner,JoelS
卡林纳抑制GSL合成2369低密度脂蛋白受体途径，表现为低密度脂蛋白受体蛋白质量增加和固醇调节元件结合蛋白表达增加。8在血管平滑肌细胞中，PDMP也被报道能增强IL-1β对亚硝酸盐的刺激，从而提供了一种额外的机制，使这种GSL在动脉粥样硬化的血管中可能是有益的。鞘磷脂生物合成途径的第一个限速步骤是丝氨酸和棕榈酰辅酶A在丝氨酸棕榈酰转移酶的催化下生成3-酮鞘氨酸。Myriocin是从板蓝根植物中分离出来的一种天然产物，它抑制这种酶并显示出免疫抑制活性。Myriocin的化学衍生化产生了一种S1P1和3受体激动剂FTY720，这是美国食品和药物管理局批准的治疗人类多发性硬化症的药物。确定FTY720是否可以延缓动脉粥样硬化的发展成为人们感兴趣的问题。在两项研究中，一项是在低密度脂蛋白受体缺陷的小鼠16中，另一项是在载脂蛋白E基因缺失的小鼠中，17 FTY720确实被报道显著减少动脉粥样硬化。随后，Poti等人报道了选择性S1P受体1型激动剂KRP-203在不影响血脂水平的情况下改善低密度脂蛋白受体−/−小鼠的动脉粥样硬化。在后一项研究中，炎症标志物的广泛减少。
Karliner Inhibition of GSL Synthesis 2369 the LDL receptor pathway as evidenced by increases in LDL receptor protein mass and elevated expression of the sterol regulatory element-binding protein. 8 In vascular smooth muscle cells, PDMP has also been reported to enhance interleukin-1β stimulation of nitrite, thereby providing an additional mechanism whereby this GSL may be of benefit in atherosclerotic vessels.The first rate-limiting step in the sphingolipid biosynthetic pathway is the formation of 3-ketosphinganine from serine and palmitoyl coenzyme A catalyzed by serine palmitoyltransferase. Myriocin, a natural product isolated from the plant Isari sinclairii, inhibits this enzyme and exhibits immunosuppressive activity. Chemical derivatization of myriocin yielded FTY720, an S1P1and 3 receptor agonist, which is an US Food and Drug Administration–approved drug for the treatment of multiple sclerosis in humans. It became of interest to determine if FTY720 could retard the development of atherosclerosis. In 2 studies, one in LDL receptor–deficient mice16 and another in ApoE null mice, 17 FTY720 was indeed reported to significantly reduce atherosclerosis. Subsequently, Poti et al18 reported that KRP-203, a selective S1P receptor type 1 agonist, ameliorated atherosclerosis in LDL receptor−/− mice without affecting lipid levels. In the latter study, there was extensive reduction of inflammatory markers.