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Tissue-specific relaxin-2 is differentially associated with the presence/size of an arterial aneurysm and the severity of atherosclerotic disease in humans
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2020-02-05 , DOI: 10.1038/s41401-019-0350-5
Konstantinos Papoutsis 1 , Alkistis Kapelouzou 2 , Georgios Georgiopoulos 3 , Christos Kontogiannis 4 , Christos Kourek 3 , Konstantinos S Mylonas 3 , Nikolaos Patelis 1 , Dennis V Cokkinos 2 , Ioannis Karavokyros 1 , Sotirios Georgopoulos 1
Affiliation  

Circulating or tissue-related biomarkers are of clinical value for risk stratification in patients with abdominal aortic aneurysms. Relaxin-2 (RL2) has been linked to the presence and size of arterial aneurysms, and to the extent of atherosclerosis in human subjects. Here, we assessed the expression levels of RL2 in aneurysmal (AA, n = 16) and atherosclerotic (ATH, n = 22) arteries, and established the correlation between RL2 levels and the presence/size of AA and the clinical severity of atherosclerosis. The expression levels of metalloproteinases (MMPs) and endothelial nitric oxide synthetase (eNOS) were also detected for correlations with different phenotypes of atherosclerosis and AA. Temporal artery biopsy specimens (n = 6) and abdominal aortic tissues harvested from accident victims during autopsy (n = 10) were used as controls. Quantitative tissue biomarker analysis revealed that tissue-specific RL2 was increased in patients with larger or symptomatic AA compared to subjects with atherosclerotic disease and healthy controls. In situ RL2 levels were proportional to the size and the severity of aneurysmatic disease, and were substantially elevated in patients with symptomatic aneurysm of any diameter or asymptomatic aneurysm of a diameter >350% of that of the normal artery. In contrast, tissue RL2 was inversely associated with the clinical severity of atherosclerotic lesions. Correlation between RL2 and MMP2 was different between ATH1 and ATH2, depending on atherosclerosis grade. Overall, tissue RL2 is differentially associated with discrete phenotypes of arterial disease and might exert multipotent biological effects on vascular wall integrity and remodeling in human subjects.



中文翻译:

组织特异性松弛素 2 与动脉瘤的存在/大小和人类动脉粥样硬化疾病的严重程度不同

循环或组织相关的生物标志物对于腹主动脉瘤患者的风险分层具有临床价值。松弛素 2 (RL2) 与动脉瘤的存在和大小以及人类受试者的动脉粥样硬化程度有关。在这里,我们评估了 RL2 在动脉瘤 (AA, n  = 16) 和动脉粥样硬化 (ATH, n  = 22) 动脉中的表达水平,并确定了 RL2 水平与 AA 的存在/大小以及动脉粥样硬化的临床严重程度之间的相关性。还检测了金属蛋白酶(MMPs)和内皮一氧化氮合成酶(eNOS)的表达水平与动脉粥样硬化和AA的不同表型的相关性。颞动脉活检标本(n = 6) 和在尸检期间从事故受害者身上采集的腹主动脉组织 ( n = 10) 用作对照。定量组织生物标志物分析显示,与患有动脉粥样硬化疾病的受试者和健康对照相比,患有较大或有症状的 AA 患者的组织特异性 RL2 增加。原位 RL2 水平与动脉瘤疾病的大小和严重程度成正比,并且在任何直径的有症状动脉瘤或直径大于正常动脉直径 350% 的无症状动脉瘤的患者中显着升高。相比之下,组织 RL2 与动脉粥样硬化病变的临床严重程度呈负相关。RL2 和 MMP2 之间的相关性在 ATH1 和 ATH2 之间是不同的,这取决于动脉粥样硬化的等级。全面的,

更新日期:2020-02-05
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