The angiopoietin receptor Tie2 is atheroprotective in arterial endothelium

Andrey Anisimov, Shentong Fang, Karthik Amudhala Hemanthakumar, Tiit Örd, Kristof van Avondt, Raphael Chevre, Anu Toropainen, Prosanta Singha, Huda Gilani, Su D. Nguyen, Sinem Karaman, Emilia A. Korhonen, Ralf H. Adams, Hellmut G. Augustin, Katariina Öörni, Oliver Soehnlein, Minna U. Kaikkonen, Kari Alitalo

Research output: Contribution to journalArticleScientificpeer-review


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 Tie2, or both Tie2 and Tie1, 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.
Original languageEnglish
JournalNature Cardiovascular Research
Issue number3
Pages (from-to)307-321
Number of pages15
Publication statusPublished - 2023
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 3121 General medicine, internal medicine and other clinical medicine

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