Possible dual role of decorin in abdominal aortic aneurysm.
Possible dual role of decorin in abdominal aortic aneurysm.
复制标题
DOI：
10.1371/journal.pone.0120689
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hamano K
中科院分区：
文献类型：
--
作者：
Ueda K;Yoshimura K;Yamashita O;Harada T;Morikage N;Hamano K
腹主动脉瘤(AAA)以慢性炎症为特征，导致细胞外基质的病理性重构。核心蛋白聚糖是一种富含亮氨酸的小重复蛋白多糖，被认为可以调节炎症和稳定细胞外基质。因此，本研究探讨核心蛋白聚糖在腹主动脉瘤发病机制中的作用。在正常情况下，核心蛋白原定位于小鼠和人的主动脉外膜。用CaCl2诱导小鼠AAA。最初，粘附素蛋白水平下降，但随着AAA的进展，所有层的粘附素水平都上升。局部应用外源性核心蛋白聚糖可阻止CaCl2诱导的AAA的发展。而Decorin在人腹主动脉壁退行性病变中高表达，且与基质金属蛋白酶-9的表达呈正相关。在细胞培养实验中，核心蛋白聚糖的加入抑制了血管平滑肌细胞分泌基质金属蛋白酶-9，但对巨噬细胞却有相反的作用。结果提示，核心蛋白在AAA中具有双重作用。正常主动脉外膜核心蛋白可能对AAA的发生有保护作用，而AAA壁中表达核心蛋白的巨噬细胞可能通过上调基质金属蛋白酶-9的分泌促进AAA的进展。
Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation, which leads to pathological remodeling of the extracellular matrix. Decorin, a small leucine-rich repeat proteoglycan, has been suggested to regulate inflammation and stabilize the extracellular matrix. Therefore, the present study investigated the role of decorin in the pathogenesis of AAA. Decorin was localized in the aortic adventitia under normal conditions in both mice and humans. AAA was induced in mice using CaCl2 treatment. Initially, decorin protein levels decreased, but as AAA progressed decorin levels increased in all layers. Local administration of exogenous decorin prevented the development of CaCl2-induced AAA. However, decorin was highly expressed in the degenerative lesions of human AAA walls, and this expression positively correlated with matrix metalloproteinase (MMP)-9 expression. In cell culture experiments, the addition of decorin inhibited secretion of MMP-9 in vascular smooth muscle cells, but had the opposite effect in macrophages. The results suggest that decorin plays a dual role in AAA. Adventitial decorin in normal aorta may protect against the development of AAA, but macrophages expressing decorin in AAA walls may facilitate the progression of AAA by up-regulating MMP-9 secretion.
登录
查看更多内容
影响因子：
1.7
作者：
Humphrey JD
通讯作者：
Humphrey JD
DOI：
10.1016/j.ejvs.2010.09.011
发表时间：
2011-01-01
影响因子：
5.7
作者：
Moll, F. L.;Powell, J. T.;Rica, J-B
通讯作者：
Rica, J-B
影响因子：
4.8
作者：
Neill, Thomas;Painter, Hannah;Iozzo, Renato V.
通讯作者：
Iozzo, Renato V.
影响因子：
1.6
作者：
Nomura, S;Yoshimura, K;Hamano, K
通讯作者：
Hamano, K
影响因子：
5.3
作者：
Al Haj Zen, Ayman;Caligiuri, Giuseppina;Lafont, Antoine
通讯作者：
Lafont, Antoine