SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration.
SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration.
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DOI：
10.1155/2016/9142425
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发表时间：
2016
影响因子：
4.6
通讯作者：
Dai QY
中科院分区：
文献类型：
--
作者：
Guo ZZ;Cao QA;Li ZZ;Liu LP;Zhang Z;Zhu YJ;Chu G;Dai QY
尼古丁是香烟的主要化学成分，在腹主动脉瘤（AAA）的发生中起着关键作用。已证实c-Jun N-末端激酶（JNK）参与弹性蛋白酶诱导的AAA。本研究旨在阐明JNK抑制剂SP 600125是否可以减弱尼古丁加血管紧张素II（AngII-）诱导的AAA形成，并评估潜在的分子机制。SP 600125显著减弱尼古丁加AngII诱导的AAA形成。基质金属蛋白酶-（MMP-）2，MMP-9，单核细胞趋化蛋白-（MCP-）1和调节激活，正常T细胞表达和分泌（RANTES）的表达在主动脉瘤病变中显著上调，但被SP 600125抑制。在体外，尼古丁以剂量依赖性方式诱导RAW 264.7（小鼠巨噬细胞）和MOVAS（小鼠血管平滑肌）细胞中MCP-1和RANTES的表达; 0.5 ng/mL尼古丁可上调表达，但500 ng/mL尼古丁可强烈下调表达。SP 600125减弱了MCP-1和RANTES表达的上调以及随后的巨噬细胞迁移。总之，SP 600125可能通过抑制MMP-2、MMP-9、MCP-1和RANTES来减弱尼古丁+AngII诱导的AAA形成。尼古丁诱导的MOVAS细胞中趋化因子的表达对RAW 264.7迁移有影响，这可能有助于尼古丁相关AAA的发展。
Nicotine, a major chemical component of cigarettes, plays a pivotal role in the development of abdominal aortic aneurysm (AAA). c-Jun N-terminal kinase (JNK) has been demonstrated to participate in elastase-induced AAA. This study aimed to elucidate whether the JNK inhibitor SP600125 can attenuate nicotine plus angiotensin II- (AngII-) induced AAA formation and to assess the underlying molecular mechanisms. SP600125 significantly attenuated nicotine plus AngII-induced AAA formation. The expression of matrix metalloproteinase- (MMP-) 2, MMP-9, monocyte chemoattractant protein- (MCP-) 1, and regulated-on-activation, normal T-cells expressed and secreted (RANTES) was significantly upregulated in aortic aneurysm lesions but inhibited by SP600125. In vitro, nicotine induced the expression of MCP-1 and RANTES in both RAW264.7 (mouse macrophage) and MOVAS (mouse vascular smooth muscle) cells in a dose-dependent manner; expression was upregulated by 0.5 ng/mL nicotine but strongly downregulated by 500 ng/mL nicotine. SP600125 attenuated the upregulation of MCP-1 and RANTES expression and subsequent macrophage migration. In conclusion, SP600125 attenuates nicotine plus AngII-induced AAA formation likely by inhibiting MMP-2, MMP-9, MCP-1, and RANTES. The expression of chemokines in MOVAS cells induced by nicotine has an effect on RAW264.7 migration, which is likely to contribute to the development of nicotine-related AAA.
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影响因子：
3.7
作者：
McGrath-Morrow SA;Hayashi M;Aherrera A;Lopez A;Malinina A;Collaco JM;Neptune E;Klein JD;Winickoff JP;Breysse P;Lazarus P;Chen G
通讯作者：
Chen G
影响因子：
82.9
作者：
Yoshimura, K;Aoki, H;Matsuzaki, M
通讯作者：
Matsuzaki, M
影响因子：
3.3
作者：
Villablanca, AC
通讯作者：
Villablanca, AC
影响因子：
4
作者：
Zhang, Xiao-Jing;He, Chengwei;Wan, Jian-Bo
通讯作者：
Wan, Jian-Bo
影响因子：
4.3
作者：
Li, Zong-Zhuang;Guo, Zhen-Zhen;Dai, Qiu-Yan
通讯作者：
Dai, Qiu-Yan