Syk activates the protective mechanism of aorta in the mouse model of aortic dissection

Autor:	Makiko Hayashi, Eichi Nakao, Yoshihiro Fukumoto, Ryohei Majima, Norifumi Nishida, Sohei Ito, Aya Furusho, Hiroki Aoki, Saki Hirakata, Y Hashimoto
Rok vydání:	2020
Předmět:	Aortic dissection Aorta business.industry Syk Inflammation Aminopropionitrile Fostamatinib medicine.disease Angiotensin II chemistry.chemical_compound chemistry medicine.artery medicine Cancer research medicine.symptom Cardiology and Cardiovascular Medicine business Aortic rupture medicine.drug
Zdroj:	European Heart Journal. 41
ISSN:	1522-9645 0195-668X
Popis:	Background Aortic dissection (AD) is a serious clinical condition that frequently results in fatal outcome. Although recent studies indicate the critical role of inflammation in AD, the molecular pathogenesis of AD is still unclear. Syk is a tyrosine kinase that regulates multiple types of inflammatory cells. Syk is also reported to regulate the function of smooth muscle cells (SMCs), the major component of aortic walls. It is unknown whether and how Syk is involved in AD pathogenesis. Objective In the current study, we investigated the role of Syk in AD. Methods and results A mouse AD model was created by continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII) that caused progressive development of AD from day 7, reaching approximately 80% of AD incidence at day 14. Western blot analysis for activated (phosphorylated) Syk (pSyk) revealed Syk activation at day 3 of BAPN+AngII infusion, followed by transient suppression at day 7, and reactivation at day 14. Double immunofluorescence staining for pSyk and smooth muscle alpha actin showed that Syk was active not only in the infiltrating inflammatory cells, but also in SMCs in AD. Treatment of mice with fostamatinib, a specific Syk inhibitor, resulted in more severe AD compared to the vehicle treatment. The AD lesion length was 3.80±0.86 mm in the vehicle group and 8.87±1.69 mm in the fostamatinib group (P Conclusions These findings uncovered the previously unrecognized role of Syk for protecting the aortic tissue in AD pathogenesis, possibly by activating the protective mechanism of aortic walls including Stat3 in SMCs. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant from Japan Society for the Promotion of Science
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::fabe6ff9a552f93c2767566f7f42574a https://doi.org/10.1093/ehjci/ehaa946.2312 Zobrazit plný text záznamu