腹主动脉瘤
基质细胞蛋白
血栓反应蛋白1
血管紧张素II
弹性蛋白
医学
载脂蛋白E
主动脉瘤
内科学
内分泌学
血栓反应素
血管平滑肌
主动脉
病理
动脉瘤
细胞外基质
金属蛋白酶
基质金属蛋白酶
生物
血管生成
外科
血压
生物化学
疾病
平滑肌
作者
Smriti M. Krishna,Sai Wang Seto,Roby J. Jose,Jiaze Li,Joseph V. Moxon,Paula Clancy,David J. Crossman,Paul Norman,Theophilus I. Emeto,Jonathan Golledge
出处
期刊:Clinical Science
[Portland Press]
日期:2017-06-01
卷期号:131 (12): 1261-1281
被引量:26
摘要
Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix (ECM) remodelling. In the present study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeated ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration (Spearman’s rho −0.129, P=0.033). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR: 0.40; 95% confidence interval (CI): 0.19–0.84, P=0.016, adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared with the relatively normal AAA neck. To further assess the role of TSP-1 in AAA initiation and progression, combined TSP-1 and apolipoprotein deficient (Thbs1−/−ApoE−/−, n=20) and control mice (ApoE−/−, n=20) were infused subcutaneously with angiotensin II (AngII) for 28 days. Following AngII infusion, Thbs1−/− ApoE−/− mice had larger AAAs by ultrasound (P=0.024) and ex vivo morphometry measurement (P=0.006). The Thbs1−/−ApoE−/− mice also showed increased elastin filament degradation along with elevated systemic levels and aortic expression of matrix metalloproteinase (MMP)-9. Suprarenal aortic segments and vascular smooth muscle cells (VSMCs) isolated from Thbs1−/−ApoE−/− mice showed reduced collagen 3A1 gene expression. Furthermore, Thbs1−/−ApoE−/− mice had reduced aortic expression of low-density lipoprotein (LDL) receptor-related protein 1. Collectively, findings from the present study suggest that TSP-1 deficiency promotes maladaptive remodelling of the ECM leading to accelerated AAA progression.
科研通智能强力驱动
Strongly Powered by AbleSci AI