Abstract 112: IL-27 Receptor Signaling Potentiates Angiotensin II Induced Myelopoiesis and Promotes Abdominal Aortic Aneurysm
| Autor: | Iuliia Peshkova, Turan Aghayev, Aliia Fatkhullina, Petr Makhov, Stephen Sykes, Ekaterina Koltsova |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 38 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvb.38.suppl_1.112 |
| Popis: | Abdominal Aortic Aneurysm (AAA) is a vascular disease, where aortic wall degradation is mediated by accumulated immune cells. Several cytokines have been suggested to play role in AAA, however the role of cytokines in immune cell accumulation and AAA progression remains poorly defined. Here we report an unexpected role of IL-27R signaling in the development of AAA. We found that in an animal model of AAA, prolonged infusion of Angiotensin (Ang) II robustly induced AAA formation in hyperlipidemic Apoe -/- and Apoe -/- Il27ra +/- mice but failed to do so in Apoe -/- Il27ra -/- mice. This mitigation of AAA formation in Apoe -/- Il27ra -/- mice was associated with a blunted accumulation of pathogenic myeloid cells in suprarenal aortas resulting from a reduction in Ang II-induced hematopoietic stem and progenitor cell (HSPCs) expansion. We found that in the absence of IL-27R signaling HSPCs were unable to fully downregulate p21 expression in response to Ang II, which impeded the ability of Apoe -/- Il27ra -/- HSPCs to proliferate. Collectively, these data demonstrate that IL-27R signaling influences AAA development by activating emergency hematopoiesis in response to elevated Ang II. Further, they provide new insights into how the immunoregulatory cytokine IL-27 drives a prominent lethal vascular disease by distant regulation of stress/emergency hematopoiesis. |
| Databáze: | OpenAIRE |
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