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Abstract：
Aortic dissection (AD) is a life-threatening condition with a high mortality rate and without effective pharmacological therapies. Our previous study illustrated that leukocyte immunoglobulin-like receptor B4 (LILRB4) knockdown promoted the contractile phenotypic switch and apoptosis of AD cells. This study aimed to further investigate the role of LILRB4 in animal models of AD and elucidate its underlying molecular mechanisms. Animal models of AD were established using 0.1% beta-aminopropionitrile and angiotensin II and an in vitro model was developed using platelet-derived growth factor BB (PDGF-BB). The effects of LILRB4 knockdown on histopathological changes, pyroptosis, phenotype transition, extracellular matrix (ECM), and Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathways were assessed using a series of in vivo and in vitro assays. The effects of the JAK2 inhibitor AG490 on AD cell function, phenotypic transition, and ECM were explored. LILRB4 was highly expressed in AD and its knockdown increased survival rate, reduced AD incidence, and alleviated histopathological changes in the AD mouse model. Furthermore, LILRB4 knockdown promoted contractile phenotype switch, stabilized the ECM, and inhibited pyroptosis. Mechanistically, LILRB4 knockdown inhibited the JAK2/STAT3 signaling pathway. JAK2 inhibitor AG490 inhibited cell viability and migration, enhanced apoptosis, induced G0/G1 cell cycle arrest, and suppressed S-phase progression in PDGF-BB-stimulated human aortic smooth muscle cells. LILRB4 knockdown suppresses AD development by inhibiting pyroptosis and the JAK2/STAT3 signaling pathway.
摘要：
主动脉夹层（AD）是一种危及生命的疾病，死亡率很高，没有有效的药物治疗。我们先前的研究表明，白细胞免疫球蛋白样受体B4（LILRB4）敲除促进了AD细胞的收缩表型转换和凋亡。本研究旨在进一步研究LILRB4在AD动物模型中的作用，并阐明其潜在的分子机制。使用0.1%β-氨基丙腈和血管紧张素II建立AD的动物模型,并且使用血小板衍生生长因子BB(PDGF-BB)建立体外模型。LILRB4敲低对组织病理学变化的影响，焦亡,表型转变，细胞外基质（ECM），和Janus激酶2（JAK2）/信号转导和转录激活因子3（STAT3）途径使用一系列体内和体外测定进行评估。JAK2抑制剂AG490对AD细胞功能的影响,表型转变，并对ECM进行了探索。LILRB4在AD中高表达，其敲除可提高生存率，降低AD发病率，并减轻AD小鼠模型的组织病理学变化。此外，LILRB4敲低促进收缩表型开关，稳定ECM，并抑制焦亡。机械上,LILRB4敲低抑制JAK2/STAT3信号通路。JAK2抑制剂AG490抑制细胞活力和迁移,细胞凋亡增强，诱导G0/G1细胞周期阻滞，并抑制PDGF-BB刺激的人主动脉平滑肌细胞的S期进展。LILRB4敲低通过抑制焦凋亡和JAK2/STAT3信号通路抑制AD的发展.
