Glucocorticoids Regulate the Vascular Remodeling of Aortic Dissection Via the p38 MAPK-HSP27 Pathway Mediated by Soluble TNF-RII.
Glucocorticoids Regulate the Vascular Remodeling of Aortic Dissection Via the p38 MAPK-HSP27 Pathway Mediated by Soluble TNF-RII.
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糖皮质激素通过可溶性 TNF-RII 介导的 p38 MAPK-HSP27 通路调节主动脉夹层的血管重塑
DOI：
10.1016/j.ebiom.2017.12.002
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发表时间：
2018-01
期刊：
影响因子：
11.1
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Zhang L;Zhou J;Jing Z;Xiao Y;Sun Y;Wu Y;Sun H
越来越多的研究表明，炎症反应参与了血管重构，在主动脉夹层的发生发展中起着重要作用。糖皮质激素因其强大而有效的抗炎作用而被广泛应用于临床。然而，糖皮质激素与主动脉夹层之间的潜在关系仍然不清楚。本研究旨在阐明糖皮质激素对主动脉夹层发生发展的影响及其可能机制。放射免疫法测定主动脉夹层患者血清皮质醇水平显著高于非破裂主动脉瘤患者和健康志愿者。在改良的C57 BL/6小鼠主动脉夹层模型中，糖皮质激素可降低主动脉夹层的发生率，并保护胶原不降解。此外，糖皮质激素还能抑制THP-1单核细胞分泌TNF-α，减少TNF-α诱导的人主动脉平滑肌细胞迁移、由收缩型向合成型的表型转换和凋亡。最后，TNF-sRII被鉴定为细胞相互作用中的重要细胞因子，其通过靶向p38 MAPK-HSP 27通路参与血管重塑。提示糖皮质激素通过减少TNF-α分泌，增加未结合的TNF-sRII，积极参与血管重构，从而抑制主动脉夹层的发生。糖皮质激素参与可溶性TNF-RII介导的主动脉夹层血管重构可溶性TNF-RII有望成为治疗主动脉夹层的潜在靶点。在临床研究中，我们发现主动脉夹层患者血清皮质醇水平明显高于非破裂主动脉瘤患者和健康志愿者。在改良的C57 BL/6小鼠模型中，我们发现糖皮质激素降低了主动脉夹层的发生率，并保护了胶原的降解。此外，糖皮质激素还能抑制巨噬细胞分泌TNF-α，减少TNF-α诱导的人主动脉平滑肌细胞迁移、由收缩型向合成型的表型转换和凋亡。糖皮质激素通过TNF-sRII介导的p38 MAPK-HSP 27通路参与主动脉夹层的血管重构。
Increasing researches suggest that inflammatory response is involved in vascular remodeling, which plays an important role in the development of aortic dissection. Glucocorticoids have been widely used in the clinical practice due to its powerful and effective anti-inflammatory property. However, the potential relationship between glucocorticoids and aortic dissection was still obscure. This study sought to elucidate the effect of glucocorticoids on the development and progression of aortic dissection, and the potential mechanism involved. Serum cortisol in aortic dissection patients was significantly higher than that in non-ruptured aortic aneurysm patients and healthy volunteers by radioimmunoassay. In modified C57BL/6 mouse model of aortic dissection, glucocorticoids reduced the incidence of aortic dissection and protected the collagen from degradation. Furthermore, glucocorticoids inhibited the TNF-α secretion of THP-1 monocytes, decreased the migration, phenotype switch from contractile type to synthetic type, and the apoptosis of human aortic smooth muscle cells induced by TNF-α. Finally, TNF-sRII was identified as an important cytokine in cellular interaction that participated in vascular remodeling by targeting the p38 MAPK-HSP27 pathway. These results indicate that glucocorticoids inhibit the incidence of aortic dissection by decreasing the TNF-α secretion and increasing the uncombined TNF-sRII, positively participating in vascular remodeling. Glucocorticoids participate in the vascular remodeling of aortic dissection mediated by soluble TNF-RII. Soluble TNF-RII may be used as a potential and attractive target for the intervention of aortic dissection in the future. In clinical study, we found the serum cortisol in aortic dissection patients was significantly higher than that in non-ruptured aortic aneurysm patients and healthy volunteers. In modified C57BL/6 mouse model, we found glucocorticoids reduced the incidence of aortic dissection, and protected the collagen from degradation. Furthermore, glucocorticoids inhibited the TNF-α secretion of macrophages, decreased the migration, the phenotype switch from contractile type to synthetic type, and the apoptosis of human aortic smooth muscle cells induced by TNF-α. In general, glucocorticoids participate the vascular remodeling of aortic dissection via the p38 MAPK-HSP27 pathway mediated by TNF-sRII.
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影响因子：
8.7
作者：
Boyle, JJ;Bowyer, DE;Bennett, MR
通讯作者：
Bennett, MR
影响因子：
2.1
作者：
Poleti, M. D.;DeRijk, R. H.;Balieiro, J. C. C.
通讯作者：
Balieiro, J. C. C.
DOI：
10.1152/ajpheart.00641.2013
发表时间：
2014-03-01
影响因子：
4.8
作者：
Rodriguez-Menocal, Luis;Faridi, Mohd Hafeez;Vazquez-Padron, Roberto I.
通讯作者：
Vazquez-Padron, Roberto I.
DOI：
10.1161/01.atv.0000033517.48444.1a
发表时间：
2002-10-01
影响因子：
8.7
作者：
Boyle, JJ;Weissberg, PL;Bennett, MR
通讯作者：
Bennett, MR
影响因子：
9.6
作者：
Marchi, Evaldo;Vargas, Francisco S.;Light, Richard W.
通讯作者：
Light, Richard W.