التفاصيل البيبلوغرافية
| العنوان: |
Abstract 13309: Protective Role of Syk in Pathogenesis of Aortic Dissection in Mice. |
| المؤلفون: |
Hashimoto, Youhei1 (AUTHOR), Aoki, Hiroki2 (AUTHOR), Fukumoto, Yoshihiro3 (AUTHOR), Ohno, Satoko3 (AUTHOR), Furusho, Aya3 (AUTHOR), Nishida, Norifumi3 (AUTHOR), Hirakata, Saki3 (AUTHOR), Hayashi, Makiko3 (AUTHOR), Majima, Ryohei3 (AUTHOR), Itou, Souhei3 (AUTHOR) |
| المصدر: |
Circulation. 2018 Supplement, Vol. 138, pA13309-A13309. 1p. |
| مصطلحات موضوعية: |
*AORTIC dissection, *ALOPECIA areata, *ANGIOTENSIN II, *PROTEIN-tyrosine kinases, *AORTIC aneurysms, *SMOOTH muscle, *MUSCLE cells |
| مستخلص: |
Aortic dissection (AD) is a serious clinical condition with unknown etiology that frequently results in fatal outcome. Recent studies showed essential role of inflammatory response both in AD and aortic aneurysm (AA), another destructive aortic disease. However, molecular pathogenesis of AD is much less characterized compared to AA. The difference of the molecular pathogenesis between AD and AA is also unclear. Very recently, we reported that Syk, a tyrosine kinase that regulates the differentiation and activation of inflammatory cells, promotes AA formation in a mouse model. In the current study, we investigated the role of Syk in AD. A mouse AD model was created by continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII), which caused AD in almost all of the mice in 2 weeks. Immunohistochemical staining for activated (phosphorylated) Syk (pSyk) revealed that Syk was inactive in normal mouse aorta, but was strongly activated in the aortic walls after AD development. Double immunofluorescence staining for pSyk and smooth muscle alpha actin showed Syk was active not only in the infiltrating inflammatory cells, but also in smooth muscle cells in AD tissue. We examined the significance of Syk activation in AD by treating mice with fostamatinib, a specific Syk inhibitor, before and during BAPN+AngII infusion. Unexpectedly, the fostamatinib-treated group developed more severe AD compared to the vehicle-treated group. Furthermore, administration of fostamatinib resulted in significantly higher mortality due to AD rupture as shown by Kaplan-Meier analysis. These findings uncovered the previously unrecognized role of Syk for the aortic tissue protection, and suggested the fundamentally different disease mechanisms of AD and AA. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
Full Text Finder