Upregulation of protein kinase cdelta in vascular smooth muscle cells promotes inflammation in abdominal aortic aneurysm.
Upregulation of protein kinase cdelta in vascular smooth muscle cells promotes inflammation in abdominal aortic aneurysm.
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血管平滑肌细胞中蛋白激酶 cdelta 的上调可促进腹主动脉瘤的炎症。
DOI：
10.1016/j.jss.2008.04.032
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Liu,Bo
中科院分区：
文献类型：
--
作者：
Schubl,Sebastian;Tsai,Shirling;Ryer,EvanJ;Wang,Chunjie;Hu,June;Kent,KCraig;Liu,Bo
背景腹主动脉瘤（AAA）的发生涉及细胞外基质降解、炎症和细胞凋亡的复杂相互作用。我们以前的研究表明，蛋白激酶Cδ（PKCδ）在氧化应激条件下的血管平滑肌细胞（vSMC）凋亡中起着关键作用。在这里，我们表明，PKCδ也参与了信号，提请炎症细胞的apneumismal tissue.MATERIALS和METHODS单核细胞趋化因子（MCP）-1和PKCδ的免疫染色进行石蜡固定的动脉切片。采用酶联免疫吸附试验检测大鼠A10细胞培养液中vSMC产生MCP-1的情况。在活化的A10细胞的培养基中评估分离的淋巴细胞的迁移。人AAA显示PKCδ的广泛和升高的表达，这在正常的主动脉组织中没有看到。细胞因子刺激培养的vSMCs可诱导关键趋化因子MCP-1的大量产生，MCP-1的表达依赖于PKCδ。刺激后的vSMCs能诱导白细胞迁移，这种作用也依赖于PKCδ活性。结论SPKC δ广泛表达于人AAA血管壁，并介导vSMC表达MCP 1，参与炎症过程。这些发现，加上早期的研究PKCδ，表明PKCδ在AAAs的发病机制中起着核心作用，并可能成为未来治疗的潜在靶点。
BACKGROUNDThe development of abdominal aortic aneurysms (AAAs) involves a complex interplay of extracellular matrix degradation, inflammation, and apoptosis. We have previously shown that protein kinase Cδ (PKCδ) plays a critical role in vascular smooth muscle cell (vSMC) apoptosis in the setting of oxidative stresses. Here, we show that PKCδ is also involved in the signaling that draws inflammatory cells to aneurismal tissue.MATERIALS AND METHODSImmunostaining for monocyte chemotactic factor (MCP)-1 and PKCδ was performed on paraffin-fixed arterial sections. Enzyme-linked immunosorbent assay to detect MCP-1 produced by vSMCs was performed on media from cultured rat A10 cells after cytokine induction with or without the PKCδ-specific inhibitor rottlerin. Migration of isolated lymphocytes was evaluated in response to media from activated A10 cells.RESULTSHuman AAAs show widespread and elevated expression of PKCδ that is not seen in normal aortic tissues. Cytokine stimulation of cultured vSMCs induced vigorous production of the key chemotactant MCP-1, the expression of which was PKCδ dependent. Stimulated vSMCs were capable of inducing the migration of leukocytes, and this effect was also dependent on PKCδ activity. Staining of human AAA tissue for MCP-1 showed an expression pattern that was identical to that of PKCδ and smooth muscle specific alpha-actin.CONCLUSIONSPKCδ is widely expressed in human AAA vessel walls and mediates MCP-1 expression by vSMCs, which could contribute to the inflammatory process. These findings, coupled with earlier studies of PKCδ, suggest that PKCδ plays a central role in the pathogenesis of AAAs and may be a potential target for future therapies.
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影响因子：
8.7
作者：
Alcorn, HG;Wolfson, SK;OLeary, D
通讯作者：
OLeary, D
ANP 抑制 TNF-α 诱导的内皮 MCP-1 表达——涉及 p38 MAPK 和 MKP-1
影响因子：
5.5
作者：
N. Weber;Signe B. Blumenthal;T. Hartung;A. Vollmar;A. Kiemer
通讯作者：
A. Kiemer
影响因子：
20.1
作者：
Rahman, A;True, AL;Malik, AB
通讯作者：
Malik, AB
主动脉瘤的血管内治疗。
影响因子：
4.4
作者：
K. Ouriel;R. Greenberg;D. Clair
通讯作者：
D. Clair
腹主动脉瘤的趋势：13 年回顾。
DOI：
10.1016/s1078-5884(05)80097-8
发表时间：
1995
期刊：
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery
影响因子：
--
作者：
A. Nasim;R. Sayers;M. Thompson;P. Healey;P. Bell
通讯作者：
P. Bell