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Expression and role of lumican in acute aortic dissection: A human and mouse study.
PLOS ONE ( IF 2.9 ) Pub Date : 2021-07-26 , DOI: 10.1371/journal.pone.0255238
Shao-Wei Chen,Shing-Hsien Chou,Ying-Chang Tung,Fu-Chih Hsiao,Chien-Te Ho,Yi-Hsin Chan,Victor Chien-Chia Wu,An-Hsun Chou,Ming-En Hsu,Pyng-Jing Lin,Winston W Y Kao,Pao-Hsien Chu

INTRODUCTION Aortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model. METHODS LUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum-/-) mice were challenged with β-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN-Ang II-challenged wildtype (WT) mice. Tgf-β/Smad2, Mmps, Lum, and Nox expression patterns were examined. RESULTS LUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum-/- AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum-/- AD mice compared with the WT AD mice. The BAPN-Ang II-challenged WT and Lum-/- AD mice had higher Tgf-β, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II-challenged WT in comparison to the unchallenged WT mice. CONCLUSION LUM expression was altered in patients with AD display increased s-LUM in blood, and Lum-/- mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes.

中文翻译:

lumican 在急性主动脉夹层中的表达和作用:一项人类和小鼠研究。

引言 主动脉夹层 (AD) 是一种危及生命的紧急情况,而 lumican (LUM) 是 AD 诊断的潜在生物标志物。我们研究了 AD 患者的 LUM 表达模式,并探讨了 Lum 在 AD 小鼠模型中的分子功能。方法 使用 AD 患者的主动脉组织分析 LUM 表达模式,并比较急性 AD (AAD) 和慢性 AD (CAD) 患者的血清可溶性 LUM (s-LUM) 水平。Lum 敲除 (Lum-/-) 小鼠用 β-氨基丙腈 (BAPN) 和血管紧张素 II (Ang II) 进行攻击以诱导 AD。将这些小鼠的存活率、AD 发病率和主动脉瘤 (AA) 与 BAPN-Ang II 攻击的野生型 (WT) 小鼠进行比较。检查了 Tgf-β/Smad2、Mmps、Lum 和 Nox 表达模式。结果 在 AAD 患者的升主动脉内膜和中膜中检测到 LUM 表达。AAD 患者的血清 s-LUM 水平显着高于 CAD。此外,Lum-/- AD 小鼠的 AD 相关死亡率和胸主动脉破裂发生率显着高于 WT AD 小鼠。然而,与 WT AD 小鼠相比,在 Lum-/- AD 小鼠中未观察到 AA 的显着病理变化。BAPN-Ang II 攻击的 WT 和 Lum-/- AD 小鼠的 Tgf-β、p-Smad2、Mmp2、Mmp9 和 Nox4 水平高于非 AD 小鼠。我们还发现,与未攻击的 WT 小鼠相比,在 BAPN-Ang II 攻击的 WT 中 Lum 表达显着更高。结论 AD 患者的 LUM 表达发生改变,血液中 s-LUM 增加,Lum-/- 小鼠表现出增强的 AD 发病机制。这些发现支持 LUM 是表示 AAD 中看到的主动脉损伤发病机制的生物标志物的观点。LUM 的存在对于维持结缔组织完整性至关重要。未来的研究应该阐明主动脉变化中 LUM 关联的潜在机制。
更新日期:2021-07-26
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