Reduction of endoplasmic reticulum stress inhibits neointima formation after vascular injury

被引:33
作者
Ishimura, Shutaro [1 ]
Furuhashi, Masato [1 ]
Mita, Tomohiro [1 ]
Fuseya, Takahiro [1 ]
Watanabe, Yuki [1 ]
Hoshina, Kyoko [1 ]
Kokubu, Nobuaki [1 ]
Inoue, Katsumi [2 ]
Yoshida, Hideaki [1 ]
Miura, Tetsuji [1 ]
机构
[1] Sapporo Med Univ, Sch Med, Dept Cardiovasc Renal & Metab Med, Chuo Ku, Sapporo, Hokkaido 0608543, Japan
[2] Kokura Mem Hosp, Dept Lab Med, Kokurakita Ku, Kitakyushu, Fukuoka 8028555, Japan
基金
日本学术振兴会;
关键词
FACTOR-KAPPA-B; BINDING PROTEIN-DELTA; FACTOR-ALPHA-RECEPTOR; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR; INTIMAL HYPERPLASIA; ACTIVATION; ER; PROLIFERATION; INFLAMMATION;
D O I
10.1038/srep06943
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Endoplasmic reticulum (ER) stress and inappropriate adaptation through the unfolded protein response (UPR) are predominant features of pathological processes. However, little is known about the link between ER stress and endovascular injury. We investigated the involvement of ER stress in neointima hyperplasia after vascular injury. The femoral arteries of 7-8-week-old male mice were subjected to wire-induced vascular injury. After 4 weeks, immunohistological analysis showed that ER stress markers were upregulated in the hyperplastic neointima. Neointima formation was increased by 54.8% in X-box binding protein-1 (XBP1) heterozygous mice, a model of compromised UPR. Knockdown of Xbp1 in human coronary artery smooth muscle cells (CASMC) in vitro promoted cell proliferation and migration. Furthermore, treatment with ER stress reducers, 4-phenylbutyrate (4-PBA) and tauroursodeoxycholic acid (TUDCA), decreased the intima-to-media ratio after wire injury by 50.0% and 72.8%, respectively. Chronic stimulation of CASMC with PDGF-BB activated the UPR, and treatment with 4-PBA and TUDCA significantly suppressed the PDGF-BB-induced ER stress markers in CASMC and the proliferation and migration of CASMC. In conclusion, increased ER stress contributes to neointima formation after vascular injury, while UPR signaling downstream of XBP1 plays a suppressive role. Suppression of ER stress would be a novel strategy against post-angioplasty vascular restenosis.
引用
收藏
页数:8
相关论文
共 33 条
[1]
ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth [J].
Bi, MX ;
Naczki, C ;
Koritzinsky, M ;
Fels, D ;
Blais, J ;
Hu, NP ;
Harding, H ;
Novoa, I ;
Varia, M ;
Raleigh, J ;
Scheuner, D ;
Kaufman, RJ ;
Bell, J ;
Ron, D ;
Wouters, BG ;
Koumenis, C .
EMBO JOURNAL, 2005, 24 (19) :3470-3481
[2]
Activation of nuclear factor-κB significantly contributes to lumen loss in a rabbit iliac artery balloon angioplasty model [J].
Breuss, JM ;
Cejna, M ;
Bergmeister, H ;
Kadl, A ;
Baumgartl, G ;
Steurer, S ;
Xu, Z ;
Koshelnick, Y ;
Lipp, J ;
De Martin, R ;
Losert, U ;
Lammer, J ;
Binder, BR .
CIRCULATION, 2002, 105 (05) :633-638
[3]
Medical Management After Coronary Stent Implantation A Review [J].
Brilakis, Emmanouil S. ;
Patel, Vishal G. ;
Banerjee, Subhash .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2013, 310 (02) :189-198
[4]
IKKβ-dependent NF-κB pathway controls vascular inflammation and intimal hyperplasia [J].
Bu, DX ;
Erl, W ;
de Martin, R ;
Hansson, GK ;
Yan, ZQ .
FASEB JOURNAL, 2005, 19 (08) :1293-+
[5]
Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2 [J].
Deng, J ;
Lu, PD ;
Zhang, YH ;
Scheuner, D ;
Kaufman, RJ ;
Sonenberg, N ;
Harding, HP ;
Ron, D .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (23) :10161-10168
[6]
Restoring endoplasmic reticulum function by chemical chaperones: an emerging therapeutic approach for metabolic diseases [J].
Engin, F. ;
Hotamisligil, G. S. .
DIABETES OBESITY & METABOLISM, 2010, 12 :108-115
[7]
Transcriptional regulation of the platelet-derived growth factor α receptor gene via CCAAT/enhancer-binding protein-δ in vascular smooth muscle cells [J].
Fukuoka, T ;
Kitami, Y ;
Okura, T ;
Hiwada, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (36) :25576-25582
[8]
The IκB Kinase Inhibitor Nuclear Factor-κB Essential Modulator-Binding Domain Peptide for Inhibition of Injury-Induced Neointimal Formation [J].
Grassia, Gianluca ;
Maddaluno, Marcella ;
Musilli, Claudia ;
De Stefano, Daniela ;
Carnuccio, Rosa ;
Di Lauro, Maria Vittoria ;
Parratt, Christopher A. ;
Kennedy, Simon ;
Di Meglio, Paola ;
Ianaro, Angela ;
Maffia, Pasquale ;
Parenti, Astrid ;
Ialenti, Armando .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2010, 30 (12) :2458-2466
[9]
PDGFβ receptor blockade inhibits intimal hyperplasia in the baboon [J].
Hart, CE ;
Kraiss, LW ;
Vergel, S ;
Gilbertson, D ;
Kenagy, R ;
Kirkman, T ;
Crandall, DL ;
Tickle, S ;
Finney, H ;
Yarranton, G ;
Clowes, AW .
CIRCULATION, 1999, 99 (04) :564-569
[10]
Regulation of vascular smooth muscle cell proliferation by nuclear factor-κB and its inhibitor, I-κB [J].
Hoshi, S ;
Goto, M ;
Koyama, N ;
Nomoto, K ;
Tanaka, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (02) :883-889