Increase of ADAM10 level in coronary artery in-stent restenosis segments in diabetic minipigs: high ADAM10 expression promoting growth and migration in human vascular smooth muscle cells via Notch 1 and 3.
Increase of ADAM10 level in coronary artery in-stent restenosis segments in diabetic minipigs: high ADAM10 expression promoting growth and migration in human vascular smooth muscle cells via Notch 1 and 3.
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DOI：
10.1371/journal.pone.0083853
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shen WF
中科院分区：
文献类型：
--
作者：
Yang K;Lu L;Liu Y;Zhang Q;Pu LJ;Wang LJ;Zhu ZB;Wang YN;Meng H;Zhang XJ;Du R;Chen QJ;Shen WF
本研究旨在确定西罗莫司洗脱支架植入糖尿病小型猪冠状动脉支架内再狭窄（ISR）发病机制中的主要蛋白质，并研究关键候选分子，特别是ADAM 10在人动脉平滑肌细胞（HASMCs）中的作用。将支架植入15只糖尿病小型猪和26只非糖尿病小型猪的冠状动脉中，并在6个月时重复血管造影。分离糖尿病小型猪中一个具有显著ISR的血管段和一个具有非ISR的血管段的内膜，并在条件培养基（CM）中培养。通过LC-MS/MS分析CM，以发现ISR中水平比非ISR组织中显著增加（≥1.5倍）的蛋白质。经过文献检索，我们集中在确定的蛋白质，其生物学功能最可能与ISR的病理生理学。其中，与非ISR对照相比，糖尿病和非糖尿病ISR组织中的ADAM 10显著增加。在细胞实验中，逆转录病毒介导的ADAM 10过表达促进HASMCs的生长和迁移。在高糖培养条件下，ADAM 10的作用比低糖培养条件下更为显著。利用shRNA和γ-分泌酶抑制剂（GSI），我们发现ADAM 10的影响部分是通过Notch 1和Notch 3途径介导的，它上调了Notch下游基因，并增强了Notch 1和Notch 3的小细胞内组分的核转位。这项研究已经确定了糖尿病小型猪ISR与非ISR节段中ADAM 10的表达显著增加，并暗示ADAM 10与糖尿病血管损伤后观察到的新生内膜形成增强有关。
This study aimed to identify major proteins in the pathogenesis of coronary artery in-stent restenosis (ISR) in diabetic minipigs with sirolimus-eluting stenting, and to investigate the roles of key candidate molecules, particularly ADAM10, in human arterial smooth muscle cells (HASMCs). The stents were implanted in the coronary arteries of 15 diabetic and 26 non-diabetic minipigs, and angiography was repeated at six months. The intima of one vascular segment with significant ISR and one with non-ISR in diabetic minipigs were isolated and cultured in conditioned medium (CM). The CM was analyzed by LC-MS/MS to uncover proteins whose levels were significantly increased (≥1.5-fold) in ISR than in non-ISR tissues. After literature searching, we focused on the identified proteins, whose biological functions were most potentially related to ISR pathophysiology. Among them, ADAM10 was significantly increased in diabetic and non-diabetic ISR tissues as compared with non-ISR controls. In cell experiments, retrovirus-mediated overexpression of ADAM10 promoted growth and migration of HASMCs. The effects of ADAM10 were more remarkable in high-glucose culture than in low-glucose culture. Using shRNA and an inhibitor of γ-secretase (GSI), we found that the influences of ADAM10 were in part mediated by Notch1 and notch 3 pathway, which up-regulated Notch downstream genes and enhanced nuclear translocation of the small intracellular component of Notch1 and Notch3. This study has identified significantly increased expression of ADAM10 in the ISR versus non-ISR segment in diabetic minipigs and implicates ADAM10 in the enhanced neointimal formation observed in diabetes after vascular injury.
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影响因子：
7
作者：
Ono, Masaya;Shitashige, Miki;Yamada, Tesshi
通讯作者：
Yamada, Tesshi
DOI：
10.1073/pnas.96.7.3922
发表时间：
1999-03-30
影响因子：
11.1
作者：
Lammich, S;Kojro, E;Fahrenholz, F
通讯作者：
Fahrenholz, F
影响因子：
4.8
作者：
Raucci, Angela;Cugusi, Simona;Bianchi, Marco E.
通讯作者：
Bianchi, Marco E.
影响因子：
6
作者：
Lindner, V;Booth, C;Liaw, L
通讯作者：
Liaw, L
DOI：
10.1016/s0735-1097(01)01579-0
发表时间：
2001-11-01
影响因子：
24
作者：
George, J;Greenberg, S;Keren, G
通讯作者：
Keren, G