Leukocytes and resident cells in the arterial wall contribute to atherosclerosis, especially at sites of disturbed blood flow. Expression of endothelial Tie1 receptor tyrosine kinase is enhanced at these sites, and attenuation of its expression reduces atherosclerotic burden and decreases inflammation. However, Tie2 tyrosine kinase function in atherosclerosis is unknown. Here we provide genetic evidence from humans and from an atherosclerotic mouse model to show that TIE2 is associated with protection from coronary artery disease. We show that deletion of , or both and , in the arterial endothelium promotes atherosclerosis by increasing Foxo1 nuclear localization, endothelial adhesion molecule expression and accumulation of immune cells. We also show that Tie2 is expressed in a subset of aortic fibroblasts, and its silencing in these cells increases expression of inflammation-related genes. Our findings indicate that unlike Tie1, the Tie2 receptor functions as the dominant endothelial angiopoietin receptor that protects from atherosclerosis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614785PMC
http://dx.doi.org/10.1038/s44161-023-00224-yDOI Listing

Publication Analysis

Top Keywords

angiopoietin receptor
8
arterial endothelium
8
tyrosine kinase
8
tie2
5
receptor tie2
4
tie2 atheroprotective
4
atheroprotective arterial
4
endothelium leukocytes
4
leukocytes resident
4
resident cells
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!