Plaque vulnerability and CHI3L1/YKL-40 in carotid atherosclerosis

• Applicant: Dr. Pavlos Tsantilas
• Subject Area: Cardiac and Vascular Surgery ; Cardiology, Angiology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 388587192

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.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Nicholas J. Leeper