The role of extracellular signal-related kinase during abdominal aortic aneurysm formation.
The role of extracellular signal-related kinase during abdominal aortic aneurysm formation.
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DOI：
10.1016/j.jamcollsurg.2012.06.414
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发表时间：
2012-11
影响因子：
5.2
通讯作者：
Upchurch, Gilbert R., Jr.
中科院分区：
文献类型：
--
作者：
Ghosh, Abhijit;DiMusto, Paul D.;Ehrlichman, Lauren K.;Sadiq, Omar;McEvoy, Brendan;Futchko, John S.;Henke, Peter K.;Eliason, Jonathan L.;Upchurch, Gilbert R., Jr.
It is hypothesized that activation of extracellular signal-related kinase (ERK) is critical in activating matrix metalloproteinases (MMPs) during abdominal aortic aneurysm (AAA) formation. C57BL/6 male mice underwent either elastase or heat-inactivated elastase aortic perfusion (n = 9 per group). Mouse aortic smooth muscle cells were transfected with ERK-1 and 2 siRNA along with or without elastase treatment. Mouse and human aortic tissue were analyzed by Western blots, zymograms, and immunohistochemistry, and statistical analysis was done using Graphpad and Image J softwares. Western blot and immunohistochemistry documented increased phospho-mitogen-activated protein kinase kinase-1/2 (pMEK-1/2; 153%, p = 0.270 by Western) and pERK (171%, p = 0.004 by Western blot) in the elastase perfused aortas. Male ERK-1−/− mice underwent elastase perfusion, and aortic diameter was determined at day 14. ERK-1−/− mice failed to develop AAA, and histologic analysis depicted intact collagen and elastin fibers in the aortas. Zymography of aortas of elastase-treated ERK-1−/− mice showed lower levels of proMMP2 (p < 0.005) and active MMP2 (p < 0.0001), as well as proMMP9 (p = 0.037) compared with C57BL/6 mice. siRNA transfection of ERK-1 and -2 significantly reduced formation of pro- and active MMP2 (p < 0.01 for both isoforms) in aortic smooth muscle cells treated with elastase in vitro. Human AAA tissue had significantly elevated levels of pMEK-1/2 (150%, p = 0.014) and pERK (159%, p = 0.013) compared with control tissues. The MAPK (mitogen-activated protein kinase)/ERK pathway is an important modulator of MMPs during AAA formation. Targeting the ERK pathway by reagents that inhibit either the expression or phosphorylation of ERK isoforms could be a potential therapy to prevent AAA formation.
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影响因子：
5.3
作者：
Kajimoto, Kan;Miyauchi, Katsumi;Daida, Hiroyuki
通讯作者：
Daida, Hiroyuki
DOI：
10.1016/j.bbapap.2005.08.017
发表时间：
2005-12-30
影响因子：
3.2
作者：
Kaminska, B
通讯作者：
Kaminska, B
DOI：
10.1523/jneurosci.6103-09.2010
发表时间：
2010-08-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Alter BJ;Zhao C;Karim F;Landreth GE;Gereau RW 4th
通讯作者：
Gereau RW 4th
影响因子：
8.8
作者：
Cuschieri, J;Maier, RV
通讯作者：
Maier, RV
影响因子：
37.8
作者：
Li, DS;Shinagawa, K;Nattel, S
通讯作者：
Nattel, S