通过JAK-STAT/HIF-1α的炎症驱动了酸通路和糖解中的代谢变化,这些变化支持大动脉细胞化
Tania Sánchez-Bayuela1, Mirian Peral-Rodrigo1, Iván Parra-Izquierdo1
1Unidad de Excelencia Instituto de Biomedicina y Genética Molecular de Valladolid (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), Spain (T.S.-B., M.P.-R., I.P.-I., C.G., O.M., E.P.-R., M.S.C., C.G.-R.).
概括
炎症会重编程细胞的新陈代谢,促进动脉疾病的进展. 准Janus酶 (JAK) 途径为这种情况提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 代谢性疾病 代谢性疾病
- 炎症研究 炎症研究
背景情况:
- 心血管疾病涉及炎症和代谢重编程,心肌细胞转移能量来源.
- 动脉疾病 (CAVD) 是一种普遍的炎症状况,缺乏有效的药理疗法.
- 在CAVD中研究促炎和代谢途径可能会揭示治疗点.
研究的目的:
- 分析潜在的炎症和新陈代谢机制 形大动脉病 (CAVD).
- 通过了解门间歇细胞 (VIC) 中的代谢重编程来确定潜在的治疗点.
主要方法:
- 使用海马,流动组学 (UPLC-MS),qPCR和代谢物量化的人类VIC的代谢分析.
- 使用基因沉默和药物抑制剂的功能丧失研究.
- 在VIC,VIC内皮细胞共同培养和人类患病的膜组织中进行验证.
主要成果:
- 炎症刺激诱导了VIC中的高糖解质程序,增加了糖解,TCA循环和酸路径流.
- 炎症VIC显示增强了糖分 ATP 生产,乳酸盐分泌和基因表达的改变,包括降低了葡萄糖-6-酸盐脱酶 (G6PD).
- 代谢重新连接对于炎症触发的化和分化至关重要,而JAK抑制剂可以逆转这些变化.
结论:
- 炎症重编程VIC代谢,降低酸通路的氧化阶段的调节,增加糖溶性流和氧化应激,促进化.
- 这些代谢变化反映了狭窄性VIC中的变化.
- 针对炎症和代谢途径,如JAK-STAT,HIF-1α和NF-κB,为CAVD提供了一个有前途的治疗途径.
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