A local proinflammatory signalling loop facilitates adverse age-associated arterial remodeling.
A local proinflammatory signalling loop facilitates adverse age-associated arterial remodeling.
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DOI：
10.1371/journal.pone.0016653
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发表时间：
2011-02-08
期刊：
影响因子：
3.7
通讯作者：
Lakatta EG
中科院分区：
文献类型：
--
作者：
Wang M;Spinetti G;Monticone RE;Zhang J;Wu J;Jiang L;Khazan B;Telljohann R;Lakatta EG
血管平滑肌细胞（VSMC）浸润和胶原蛋白沉积在弥漫性增厚的内膜内的一致性是伴随年龄增长的中央动脉壁炎症的显著特征。然而，所涉及的分子机制仍不明确。大鼠主动脉的免疫染色和免疫印迹显示，随着年龄的增长，主动脉壁内的促炎分子MCP-1、TGF-β1和MMP-2三联体增加。将从8月龄大鼠（年轻）分离的VSMC暴露于MCP-1作用，通过CCR-2信号传导，TGF-β1活性增加，达到30月龄（老年）大鼠未处理VSMC的水平，同时MMP-2活化增加。此外，年轻的VSMC暴露于TGF-β1使MCP-1和MMP-2活化水平增加至来自老年大鼠的未经处理的VSMC的水平。这种增强VSMC的胶原蛋白产生和侵袭性的自催化信号传导回路被Si-MCP-1（一种CCR 2拮抗剂）或MMP-2抑制有效地抑制。MCP-1、MMP-2或TGF-β1活性的阈值水平触发前馈信号传导机制，该机制与年龄相关的不良动脉壁重塑的开始和进展有关。抑制这种信号循环的干预可能会潜在地延缓与年龄相关的不良动脉重塑。
The coincidence of vascular smooth muscle cells (VSMC) infiltration and collagen deposition within a diffusely thickened intima is a salient feature of central arterial wall inflammation that accompanies advancing age. However, the molecular mechanisms involved remain undefined. Immunostaining and immunoblotting of rat aortae demonstrate that a triad of proinflammatory molecules, MCP-1, TGF-β1, and MMP-2 increases within the aortic wall with aging. Exposure of VSMC isolated from 8-mo-old rats (young) to MCP-1 effects, via CCR-2 signaling, both an increase in TGF-β1 activity, up to levels of untreated VSMC from 30-mo-old (old) rats, and a concurrent increase in MMP-2 activation. Furthermore, exposure of young VSMC to TGF-β1 increases levels of MCP-1, and MMP-2 activation, to levels of untreated VSMC from old rats. This autocatalytic signaling loop that enhances collagen production and invasiveness of VSMC is effectively suppressed by si-MCP-1, a CCR2 antagonist, or MMP-2 inhibition. Threshold levels of MCP-1, MMP-2, or TGF-β1 activity trigger a feed-forward signaling mechanism that is implicated in the initiation and progression of adverse age-associated arterial wall remodeling. Intervention that suppressed this signaling loop may potentially retard age-associated adverse arterial remodeling.
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影响因子：
3.2
作者：
Wang M;Monticone RE;Lakatta EG
通讯作者：
Lakatta EG
主动脉Calpain-1活性增加可介导与年龄相关的血管紧张素II信号的血管平滑肌细胞信号传导。
影响因子：
3.7
作者：
Jiang, Liqun;Wang, Mingyi;Zhang, Jing;Monticone, Robert E.;Telljohann, Richard;Spinetti, Gaia;Pintus, Gianfranco;Lakatta, Edward G.
通讯作者：
Lakatta, Edward G.
影响因子：
29.4
作者：
Inagaki, Yutaka;Higashi, Kiyoshi;Okazaki, Isao
通讯作者：
Okazaki, Isao
影响因子：
6
作者：
Wang, MY;Zhang, J;Lakatta, EG
通讯作者：
Lakatta, EG
DOI：
10.1084/jem.20050607
发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Filippov S;Koenig GC;Chun TH;Hotary KB;Ota I;Bugge TH;Roberts JD;Fay WP;Birkedal-Hansen H;Holmbeck K;Sabeh F;Allen ED;Weiss SJ
通讯作者：
Weiss SJ