Plaque vulnerability and CHI3L1/YKL-40 in carotid atherosclerosis

颈动脉斑块易损性和斑块破裂在缺血性卒中的发病机制中起重要作用。因此，人们致力于确定斑块易损性的分子和病理生理学特征。薄薄或破碎的富含SMC的纤维帽被认为是脆弱斑块的关键特征。一种称为几丁质酶3-样-1(CHI3L1-又称YKL-40)的蛋白质被发现在SMC的增殖和迁移中发挥关键作用。在初步工作中，我们已经能够定位CHI3L1，它在SMC中丰富，并在脆弱病变的纤维帽中高表达。因此，本研究项目的目的是进一步研究CHI3L1在晚期颈动脉粥样硬化斑块中调控SMC可塑性的作用。对于功能研究，我们计划使用宿主实验室的两个成熟的动物模型来评估CHI3L1在体内颈动脉斑块中的作用。此外，体外分析的目的是确定CHI3L1调节如何影响培养的血管SMC细胞命运决定的机制。

Plaque vulnerability and plaque rupture in the carotid artery play an important role in the pathogenesis of an ischemic stroke. Therefore, efforts have been devoted to determine the molecular and pathophysiological characteristics of plaque vulnerability. A thin or disrupted smooth muscle cell (SMC)–rich fibrous cap is considered to be a crucial feature of a vulnerable plaque. A protein called Chitinase 3-like-1 (CHI3L1 - also known as YKL-40) has been identified to potentially play a key role in SMC proliferation and migration. In preliminary work, we were already able to locate CHI3L1 as enriched in SMCs and highly expressed in fibrous caps of vulnerable lesions. The aim of this research project is therefore to further investigate the role of CHI3L1 in steering SMC plasticity in advanced carotid atherosclerotic plaques. For functional studies, we plan to use two well established animal models of the host laboratory to evaluate the role of CHI3L1 in carotid plaques in vivo. Additionally, in vitro analysis aims to define mechanisms how CHI3L1 modulation effects cell fate decisions in cultured vascular SMCs.