ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis.
ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis.
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DOI：
10.1038/s41598-017-03573-4
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发表时间：
2017-06-16
影响因子：
4.6
通讯作者：
Gonçalves I
中科院分区：
文献类型：
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作者：
Bengtsson E;Hultman K;Dunér P;Asciutto G;Almgren P;Orho-Melander M;Melander O;Nilsson J;Hultgårdh-Nilsson A;Gonçalves I
几项大规模的全基因组关联研究已经确定了A去整合素和金属蛋白酶与血栓形成蛋白1型重复序列（ADAMTS）-7基因组区域的单核苷酸多态性与冠状动脉疾病的关联。实验研究提供了ADAMTS-7在损伤诱导的血管新生内膜形成和动脉粥样硬化病变发展中的功能作用的证据。然而，ADAMTS-7是否与人类的特定斑块表型相关尚未研究。通过免疫组化分析了有和无脑血管症状患者的颈动脉斑块（n = 206）中ADAMTS-7的表达，并将其与斑块易损性相关的成分相关联。与无症状患者的病变相比，有症状患者的斑块显示ADAMTS-7水平升高。高水平的ADAMTS-7与高水平的CD 68染色和脂质含量相关，但与低平滑肌细胞和胶原蛋白含量相关，这些共同是易损斑块表型的特征。ADAMTS-7水平高于中位数与术后心血管事件风险增加相关。我们的数据显示ADAMTS-7与人颈动脉病变中的易损斑块表型相关。这些数据支持先前观察到的ADAMTS-7的潜在致动脉粥样硬化作用。
Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of atherosclerotic lesions. However, whether ADAMTS-7 is associated with a specific plaque phenotype in humans has not been investigated. Carotid plaques (n = 206) from patients with and without cerebrovascular symptoms were analyzed for expression of ADAMTS-7 by immunohistochemistry and correlated to components associated with plaque vulnerability. Plaques from symptomatic patients showed increased levels of ADAMTS-7 compared with lesions from asymptomatic patients. High levels of ADAMTS-7 correlated with high levels of CD68-staining and lipid content, but with low smooth muscle cell and collagen content, which together are characteristics of a vulnerable plaque phenotype. ADAMTS-7 levels above median were associated with increased risk for postoperative cardiovascular events. Our data show that ADAMTS-7 is associated with a vulnerable plaque phenotype in human carotid lesions. These data support previous observations of a potential proatherogenic role of ADAMTS-7.