Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou, 510260, People's Republic of China.
Mol Cell Biochem. 2014 Jan;385(1-2):199-205. doi: 10.1007/s11010-013-1828-y. Epub 2013 Sep 25.
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.
新出现的证据表明，血浆 C 反应蛋白（CRP）水平升高或胰岛素样生长因子 1（IGF-1）浓度降低可能分别与冠状动脉疾病或心肌梗死风险增加相关。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）激活的作用。我们发现 IGF-1 可挽救内皮型一氧化氮合酶的活性并降低 EC 中细胞间黏附分子-1 和血管细胞黏附分子-1 的释放。我们还表明，IGF-1 通过激活 PI3K/Akt 途径和抑制 JNK/c-Jun 和 MAPK p38/ATF2 信号通路来拮抗 CRP 的作用，而不是抑制 ERK1/2 活性。这些发现为内皮细胞激活的生理病理机制提供了证据，并为 IGF-1 的保护特性提供了新的见解。
