Insulin-like growth factor 1 opposes the effects of C-reactive protein on endothelial cell activation
Insulin-like growth factor 1 opposes the effects of C-reactive protein on endothelial cell activation
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胰岛素样生长因子 1 对抗 C 反应蛋白对内皮细胞活化的影响
DOI：
10.1007/s11010-013-1828-y
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发表时间：
2014-01-01
影响因子：
4.3
通讯作者：
Liu, Shi-Ming
中科院分区：
文献类型：
--
作者：
Liu, Shao-Jun;Zhong, Yun;Liu, Shi-Ming
新出现的证据表明，高血浆C-反应蛋白（CRP）水平或低血浆胰岛素样生长因子1（IGF-1）浓度可能分别与冠状动脉疾病或心肌梗死的风险增加。有趣的是，动物模型研究和流行病学调查表明，循环IGF-1和CRP水平呈负相关。本研究旨在评估IGF-1是否可以直接对抗CRP对内皮细胞（EC）活化的影响。我们发现，IGF-1拯救内皮型一氧化氮合酶的活性，并减少释放细胞间粘附分子-1和血管细胞粘附分子-1从EC。我们还发现，IGF-1通过激活PI 3 K/Akt通路并抑制JNK/c-Jun和MAPK p38/ATF 2信号通路而不是抑制ERK 1/2活性来拮抗CRP的作用。这些发现提供了内皮细胞活化的病理生理机制的证据，并对IGF-1的保护特性提供了新的见解。
Emerging evidence demonstrates that high plasma C-reactive protein (CRP) levels or low plasma insulin-like growth factor 1 (IGF-1) concentrations may be separately associated with the increased risk of coronary artery disease or myocardial infarction. Interestingly, animal model studies and epidemiological investigations indicate that circulating IGF-1 and CRP levels have an inverse correlation. The present study aims to evaluate if IGF-1 can directly oppose the effects of CRP on endothelial cell (EC) activation. We found that IGF-1 rescues endothelial nitric oxide synthase activity and decreases the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. We also showed that IGF-1 antagonizes the effects of CRP by activating the PI3K/Akt pathway and suppressing the JNK/c-Jun and MAPK p38/ATF2 signaling pathways, rather than inhibiting ERK1/2 activity. These findings provide evidence of the physiopathological mechanisms of endothelial activation and novel insights into the protective properties of IGF-1.