Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade.
Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade.
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菊苣酸通过抑制 ROS/NF kappa B/mTOR/P70S6K 信号级联来防止 PDGF-BB 诱导的 VSMC 去分化、增殖和迁移
DOI：
10.1016/j.redox.2017.11.012
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发表时间：
2018-04
期刊：
影响因子：
11.4
通讯作者：
Sun HJ
中科院分区：
文献类型：
--
作者：
Lu QB;Wan MY;Wang PY;Zhang CX;Xu DY;Liao X;Sun HJ
血管平滑肌细胞（vascular smooth muscle cells，VSMC）表型转换是指VSMC合成标志物表达增加，收缩标志物表达减少，是血管平滑肌细胞增殖和迁移的重要环节，在动脉粥样硬化等心血管疾病的发生、发展过程中起重要作用。菊苣酸（CA）被认为具有强大的心血管保护作用。然而，关于CA对VSMC生物学的影响知之甚少。在此，在培养的VSMC，我们表明，预处理与CA剂量依赖性抑制血小板衍生生长因子BB型（PDGF-BB）诱导的VSMC表型改变，增殖和迁移。在机制上，PDGF-BB处理的VSMCs表现出更高的哺乳动物雷帕霉素靶蛋白（mTOR）和P70 S6 K磷酸化，CA预处理，氯化二苯碘铵（DPI），活性氧（ROS）清除剂N-乙酰基-L-半胱氨酸（NAC）和核因子-κB（NFκB）抑制剂Bay 117082减弱了这一点。CA可抑制PDGF-BB引发的ROS生成和p65-NFκB活化。此外，NAC和DPI均能抑制PDGF-BB诱导的p65-NFκB核转位、I κBα（IκBα）的磷酸化和降解。值得注意的是，阻断ROS/NFκB/mTOR/P70 S6 K信号级联反应可阻止PDGF-BB诱导的VSMC表型转化、增殖和迁移。CA治疗可防止大鼠颈动脉结扎模型中的内膜增生和血管重塑。结果提示，CA通过抑制ROS/NFκB/mTOR/P70 S6 K信号通路，抑制PDGF-BB诱导的VSMC表型转换、增殖、迁移和新生内膜形成。菊苣酸减弱PDGF-BB诱导的VSMC表型转化、增殖和迁移。菊苣酸可拮抗VSMCs激活的ROS/NFκB/mTOR/P70 S6 K信号通路。菊苣酸治疗可预防大鼠颈动脉结扎模型中的内膜增生。
Phenotypic switch of vascular smooth muscle cells (VSMCs) is characterized by increased expressions of VSMC synthetic markers and decreased levels of VSMC contractile markers, which is an important step for VSMC proliferation and migration during the development and progression of cardiovascular diseases including atherosclerosis. Chicoric acid (CA) is identified to exert powerful cardiovascular protective effects. However, little is known about the effects of CA on VSMC biology. Herein, in cultured VSMCs, we showed that pretreatment with CA dose-dependently suppressed platelet-derived growth factor type BB (PDGF-BB)-induced VSMC phenotypic alteration, proliferation and migration. Mechanistically, PDGF-BB-treated VSMCs exhibited higher mammalian target of rapamycin (mTOR) and P70S6K phosphorylation, which was attenuated by CA pretreatment, diphenyleneiodonium chloride (DPI), reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) and nuclear factor-κB (NFκB) inhibitor Bay117082. PDGF-BB-triggered ROS production and p65-NFκB activation were inhibited by CA. In addition, both NAC and DPI abolished PDGF-BB-evoked p65-NFκB nuclear translocation, phosphorylation and degradation of Inhibitor κBα (IκBα). Of note, blockade of ROS/NFκB/mTOR/P70S6K signaling cascade prevented PDGF-BB-evoked VSMC phenotypic transformation, proliferation and migration. CA treatment prevented intimal hyperplasia and vascular remodeling in rat models of carotid artery ligation in vivo. These results suggest that CA impedes PDGF-BB-induced VSMC phenotypic switching, proliferation, migration and neointima formation via inhibition of ROS/NFκB/mTOR/P70S6K signaling cascade. Chicoric acid attenuated PDGF-BB-evoked VSMC phenotypic transformation, proliferation and migration. Chicoric acid antagonized the activated ROS/NFκB/mTOR/P70S6K signaling pathway in VSMCs. Chicoric acid treatment prevented intimal hyperplasia in rat models of carotid artery ligation.
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DOI：
10.1016/j.bbrc.2015.05.097
发表时间：
2015-08-14
影响因子：
3.1
作者：
Ha, Jung Min;Yun, Sung Ji;Bae, Sun Sik
通讯作者：
Bae, Sun Sik
影响因子：
7.4
作者：
Al Ghouleh, Imad;Khoo, Nicholas K. H.;Knaus, Ulla G.;Griendling, Kathy K.;Touyz, Rhian M.;Thannickal, Victor J.;Barchowsky, Aaron;Nauseef, William M.;Kelley, Eric E.;Bauer, Phillip M.;Darley-Usmar, Victor;Shiva, Sruti;Cifuentes-Pagano, Eugenia;Freeman, Bruce A.;Gladwin, Mark T.;Pagano, Patrick J.
通讯作者：
Pagano, Patrick J.
DOI：
10.1084/jem.20102049
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bulua AC;Simon A;Maddipati R;Pelletier M;Park H;Kim KY;Sack MN;Kastner DL;Siegel RM
通讯作者：
Siegel RM
影响因子：
11.4
作者：
Escribano-Lopez, Irene;Diaz-Morales, Noelia;Rovira-Llopis, Susana;de Maranon, Arantxa Martinez;Orden, Samuel;Alvarez, Angeles;Banuls, Celia;Rocha, Milagros;Murphy, Michael P.;Hernandez-Mijares, Antonio;Victor, Victor M.
通讯作者：
Victor, Victor M.
补充菊苣酸可通过抑制 NF-κ B 预防全身炎症引起的记忆障碍和淀粉样蛋白生成
影响因子：
4.8
作者：
Liu, Qian;Chen, Yuwei;Liu, Xuebo
通讯作者：
Liu, Xuebo