IGF-1调控平滑肌细胞维持血管稳态在颅内动脉瘤发生发展中的作用及相关分子机制

颅内动脉瘤（IA）被喻为脑内的“不定时炸弹”。研究表明其与异常血流动力学引起的血管稳态失调有密切关系。血管平滑肌细胞（VSMCs）是调节血管稳态的主要细胞，异常血流动力学刺激下会发生表型变化促进IA的发生。IGF-1（胰岛素样生长因子-1）被报道具有调节VSMCs的功能，从而对血管起保护作用。我们前期发现IGF-1及其上游调控因子FOXM1在IA模型初期显著高表达，但IGF-1在IA中的作用如何还尚待明确。因此，本项目拟围绕“IGF-1在IA的发生发展中起预防和保护作用”展开，包括：1）动物实验研究IGF-1的过表达和干扰对异常血流动力学诱导的IA的防治作用；2）体外研究VSMCs在异常血流动力学刺激下，IGF-1对其表型维持作用以及验证FOXM1对IGF-1的转录调控作用。本研究旨在阐明IGF-1对异常血流动力学诱导IA发生发展的血管稳态的维持作用以及机制，为IA的防治策略提供新的思路。

Intracranial aneurysms (IAs) are described as "Untimed Bombs" in the brain. Previous study showed that it was closely related to altered blood vessel homeostasis caused by abnormal hemodynamics. Vascular smooth muscle cells (VSMCs) are the main cells that regulate the homeostasis of blood vessels, so abnormal hemodynamics will induce phenotypic changes of VSMCs to promote the occurrence of IA. IGF-1 (insulin-like growth factor -1) has been reported to inhibit the apoptosis and promote proliferation of VSMCs, leading to protect the blood vessels. We have found that IGF-1 and its upstream regulator FOXM1 were highly expressed at the early stage of the IA rabbit model, however, the role of IGF-1 in IA occurrence and development  remained to be clear. Therefore, in this project we plan to focus on the preventive and protective role of IGF-1 in IA occurrence and development. The main research will include: 1) animal study: exploring prevention and treatment effect of IGF-1 overexpression and interference on IA; 2) in vitro study: phenotypic maintenance effect of IGF-1 on VSMCs under stimulation of abnormal hemodynamics; confirmation of transcription regulation effect of FOXM1 on IGF-1. This study aims to elucidate the maintenance effect and mechanism of IGF-1 on vascular homeostasis induced by abnormal hemodynamics in the development of IA and provide new ideas for IA prevention and treatment strategies.