title: Interleukin-1/toll-like receptor-induced nuclear factor kappa B signaling participates in intima hyperplasia after carotid artery balloon injury in goto-kakizaki rats: a potential target therapy pathway.
abstract: The value of restenosis after percutaneous coronary intervention (PCI) is recognized worldwide, especially for diabetic patients. Interleukin-1/Toll-like receptor (IL-1/TLR) signaling is involved in innate and adaptive immune responses, but whether and how the IL-1/TLR-induced nuclear factor kappa B (NFκB) pathway plays key roles in intimal formation is unclear. The underlying mechanism of intima hyperplasia was investigated with a model of carotid balloon injury in Goto-Kakizaki (GK) and Wistar rats and with lipopolysaccharide-stimulated macrophages. Elastic-van Gieson staining showed the medial area peakedon Day 3 post-injury and decreased by Day 7 post-injury in both GK and Wistar rats. The N/M at Day 7 in GK rats was significantly higher than in Wistar rats (p<0.001). The percent of 5-ethynyl-2'-deoxyuridine (EdU) staining-positive cells on Day 3 post-injury was greater than seen on Day 7 post-injury in GK and Wistar rats. The percent of EdU-positive cells on Days 3 and 7 post-injury in Wistar rats was less than that found in GK rats (p<0.01; p<0.05). NFκBp65 immunostaining had increased by Day 7 post-injury. Agilent Whole Genome Oligo Microarray verified that the IL-1/TLR-induced NFκB pathway was activated by carotid balloon injury. TLR4, IL-1 receptor associated kinase, inhibitors α of NFκB, human antigen R, c-Myc (Proto-Oncogene Proteins), EGF-like module-containing mucin-like hormone receptor-like 1 and Interleukin-6 were up-regulated or down-regulated according to immunochemistry, quantitative real-time PCR, Western blotting and Enzyme linked immunosorbent assay. Overall, we conclude that the IL-1/TLR-induced NFκB pathway participates in the intimal hyperplasia after carotid injury in GK and Wistar rats and that GK rats respond more intensely to the inflammation than Wistar rats.
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Jiangsu Province, P. R. China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Jiangsu Province, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Jiangsu Province, P. R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Hu
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Jiangsu Province, P. R. China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Aultman Hospital & Canton Medical Education Foundation, Northeast Ohio Medical University, Canton, Ohio, United States of America.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Cardiology of Affiliated Hospital of Xuzhou Medical College, Jiangsu Province, P. R. China.
authors.forename: Defeng
authors.initials: D
authors.lastname: Pan
authors.affiliation: Cardiology of Affiliated Hospital of Xuzhou Medical College, Jiangsu Province, P. R. China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Wu
authors.affiliation: Cardiology of Affiliated Hospital of Xuzhou Medical College, Jiangsu Province, P. R. China.
authors.forename: Tongda
authors.initials: T
authors.lastname: Xu
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism*; D006965:Hyperplasia / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism*; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology*
chemical_list: D007375:Interleukin-1; C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D051193:Toll-Like Receptors
references.citation: Horm Metab Res. 2007 Aug;39(8):567-74
references.pmid: 17712721
references.citation: J Am Coll Cardiol. 1998 Jan;31(1):224-30
references.pmid: 9426044
references.citation: Acta Med Indones. 2009 Jan;41(1):41-4
references.pmid: 19258681
references.citation: Int J Clin Exp Med. 2010 Jul 15;3(3):192-201
references.pmid: 20827317
references.citation: Eur Heart J. 2008 Nov;29(22):2733-41
references.pmid: 18832385
references.citation: Gene Ther. 2004 Aug;11(16):1273-82
references.pmid: 15175640
references.citation: Am J Pathol. 1997 Oct;151(4):1085-95
references.pmid: 9327742
references.citation: Cell. 2002 May 3;109(3):321-34
references.pmid: 12015982
references.citation: J Immunol. 2000 Jan 15;164(2):558-61
references.pmid: 10623794
references.citation: FASEB J. 2005 Aug;19(10):1293-5
references.pmid: 15939736
references.citation: Diabetes. 2002 Jun;51(6):1793-804
references.pmid: 12031967
references.citation: Adv Exp Med Biol. 1988;246:29-31
references.pmid: 3074659
references.citation: Med Eng Phys. 2011 Mar;33(2):148-63
references.pmid: 21075668
references.citation: Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2630-7
references.pmid: 17008589
references.citation: Mol Cell Biol. 2003 Oct;23(20):7177-88
references.pmid: 14517288
references.citation: Clin Res Cardiol. 2006 Jan;95 Suppl 1:i18-26
references.pmid: 16598543
references.citation: J Biol Chem. 2008 Nov 14;283(46):31697-705
references.pmid: 18794297
references.citation: Heart Vessels. 2008 Mar;23(2):75-82
references.pmid: 18389330
references.citation: J Mol Med (Berl). 2011 Jun;89(6):545-53
references.pmid: 21279500
references.citation: Diabetes. 2010 Dec;59(12):3240-6
references.pmid: 20876710
references.citation: Circulation. 2004 Jun 15;109(23):2844-9
references.pmid: 15173029
references.citation: J Am Coll Cardiol. 2000 Jan;35(1):157-63
references.pmid: 10636274
references.citation: Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1944-9
references.pmid: 19661481
references.citation: Diabetes Metab Res Rev. 2005 Nov-Dec;21(6):495-504
references.pmid: 15926190
references.citation: Tohoku J Exp Med. 1976 May;119(1):85-90
references.pmid: 951706
references.citation: Curr Cardiol Rep. 2013 Jan;15(1):323
references.pmid: 23250660
references.citation: J Exp Med. 2007 May 14;204(5):1025-36
references.pmid: 17470642
references.citation: J Endovasc Ther. 2001 Oct;8(5):477-83
references.pmid: 11718406
references.citation: Expert Rev Cardiovasc Ther. 2004 Sep;2(5):653-60
references.pmid: 15350167
references.citation: Circ Res. 1999 Sep 17;85(6):524-33
references.pmid: 10488055
references.citation: Cardiovasc Diabetol. 2012 Dec 13;11:150
references.pmid: 23237526
references.citation: Int J Cardiol. 2013 Sep 20;168(1):197-206
references.pmid: 23063477
references.citation: Atherosclerosis. 2002 Mar;161(1):153-9
references.pmid: 11882327
references.citation: Inflamm Res. 2013 Feb;62(2):173-9
references.pmid: 23104275
references.citation: Am J Cardiol. 2006 Sep 4;98(5A):14J-18J
references.pmid: 16931201
references.citation: Circulation. 1999 Jan 5-12;99(1):44-52
references.pmid: 9884378
references.citation: Ann Intern Med. 2003 Nov 18;139(10):824-34
references.pmid: 14623620
references.citation: PLoS Genet. 2012 Sep;8(9):e1002977
references.pmid: 23028373
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14
references.pmid: 9482916
references.citation: Biochem Biophys Res Commun. 2007 Mar 2;354(1):45-9
references.pmid: 17210129
references.citation: Cell Death Differ. 2006 May;13(5):816-25
references.pmid: 16410796
references.citation: PLoS One. 2010 Aug 23;5(8):e12323
references.pmid: 20808802
references.citation: J Biol Chem. 2001 Mar 30;276(13):10229-33
references.pmid: 11150311
references.citation: J Leukoc Biol. 2004 Oct;76(4):904-8
references.pmid: 15258191
references.citation: J Immunol. 2011 Aug 1;187(3):1458-66
references.pmid: 21709150
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R673-80
references.pmid: 18094066
references.citation: Vasc Health Risk Manag. 2005;1(1):73-8
references.pmid: 17319099