Gal-1 (Galectin-1) Upregulation Contributes to Abdominal Aortic Aneurysm Progression by Enhancing Vascular Inflammation
Gal-1 (Galectin-1) Upregulation Contributes to Abdominal Aortic Aneurysm Progression by Enhancing Vascular Inflammation
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DOI：
10.1161/atvbaha.120.315398
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发表时间：
2021-01-01
影响因子：
8.7
通讯作者：
Chau, Lee-Young
中科院分区：
文献类型：
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作者：
Chiang, Ming-Tsai;Chen, I-Ming;Chau, Lee-Young
目的：腹主动脉瘤（AAA）是一种血管退行性疾病，可导致主动脉突然破裂，老年人死亡率高。然而，没有预后和治疗目标可用于疾病管理。Gal-1（galectin-1）是一种β-半乳糖苷结合凝集素，在血管系统中组成性表达，具有维持血管稳态的作用。本研究旨在探讨潜在的参与Gal-1在AAA progression.Approach和结果：Gal-1显着升高血管紧张素II（血管紧张素II）输注apoE缺陷小鼠发展AAA的循环和主动脉组织。Gal-1缺乏可降低AAA的发生率和严重程度，降低主动脉基质金属蛋白酶（MMP）和促炎细胞因子的表达。TNF α（肿瘤坏死因子α）诱导培养的血管平滑肌细胞和外膜成纤维细胞中Gal-1的表达。Gal-1缺失增强了TNF α诱导的成纤维细胞MMP 9的表达，但对血管平滑肌细胞无影响。半胱氨酰标记实验表明，主动脉Gal-1在体内表现出氧化敏感性。重组氧化Gal-1通过激活MAP（mitogen-activated protein）激酶信号通路在不同程度上诱导巨噬细胞、血管平滑肌细胞和成纤维细胞中MMP 9和炎性细胞因子的表达。临床上，血清MMP 9水平显着高于在两个AAA和冠状动脉疾病患者比对照组，而血清Gal-1水平升高的AAA患者，但不冠状动脉疾病时，与controls.Conclusions相比：Gal-1是高度诱导，并有助于AAA通过增强基质降解活性和炎症反应的实验模型。在人类患者中也观察到Gal-1和AAA之间的病理联系。这些发现支持Gal-1作为AAA的疾病生物标志物和治疗靶点的潜力。
Objective: Abdominal aortic aneurysm (AAA) is a vascular degenerative disease causing sudden rupture of aorta and significant mortality in elders. Nevertheless, no prognostic and therapeutic target is available for disease management. Gal-1 (galectin-1) is a beta -galactoside-binding lectin constitutively expressed in vasculature with roles in maintaining vascular homeostasis. This study aims to investigate the potential involvement of Gal-1 in AAA progression.Approach and Results: Gal-1 was significantly elevated in circulation and aortic tissues of Ang II (angiotensin II)-infused apoE-deficient mice developing AAA. Gal-1 deficiency reduced incidence and severity of AAA with lower expression of aortic MMPs (matrix metalloproteases) and proinflammatory cytokines. TNF alpha (tumor necrosis factor alpha) induced Gal-1 expression in cultured vascular smooth muscle cells and adventitial fibroblasts. Gal-1 deletion enhanced TNF alpha -induced MMP9 expression in fibroblasts but not vascular smooth muscle cells. Cysteinyl-labeling assay demonstrated that aortic Gal-1 exhibited susceptibility to oxidation in vivo. Recombinant oxidized Gal-1 induced expression of MMP9 and inflammatory cytokines to various extents in macrophages, vascular smooth muscle cells, and fibroblasts through activation of MAP (mitogen-activated protein) kinase signaling. Clinically, serum MMP9 level was significantly higher in both patients with AAA and coronary artery disease than in control subjects, whereas serum Gal-1 level was elevated in patients with AAA but not coronary artery disease when compared with controls.Conclusions: Gal-1 is highly induced and contributes to AAA by enhancing matrix degradation activity and inflammatory responses in experimental model. The pathological link between Gal-1 and AAA is also observed in human patients. These findings support the potential of Gal-1 as a disease biomarker and therapeutic target of AAA.