title: Smooth muscle cells from the anastomosed artery are the major precursors for neointima formation in both artery and vein grafts.
abstract: Accumulation of smooth muscle cells (SMC) results in neointima formation in injured vessels. Two graft models consisting of vein and artery grafts were created by anastomosing common carotid arteries to donor vessels. To identify the origin of the neointima cells from anastomosed arteries, we use Wnt1-Cre/reporter mice to label and track SMCs in the common carotid artery. The contribution of SMCs in the neighboring arteries to neointima formation was studied. On evaluating the artery grafts after 1 month, >90 % of the labeled neointima cells were found to have originated from the anastomosing host arteries. Most of the neointima cells were also smooth muscle α-actin positive (SMA-α(+)) and expressed the smooth muscle myosin heavy chain (SMMHC), the SMC terminal differentiation marker. In vein grafts, about 60 % SMA-α-positive cells were from anastomosing arteries. Bone marrow cells did not contribute to neointima SMCs in vein grafts, but did co-stain with markers of inflammatory cells. Wnt1 expression was not detected in the neointima cells in the vein or artery grafts, or the injured femoral arteries. Neointima SMCs showed the synthetic phenotype and were positively labeled with BrdU in vitro and in vivo. Treatment with the IGF-1 receptor inhibitor suppressed SMC proliferation and neointima formation in vein grafts. Our results indicate that SMCs from the neighboring artery are predominantly present in the neointima formed in both vein and artery grafts and that Wnt1-Cre mice can be used to explore the role of SMCs originating from neighboring vessels in vascular remodeling.
authors.affiliation: Department of Nephrology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liang
authors.forename: Anlin
authors.initials: A
authors.lastname: Liang
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.forename: Jizhong
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000714:Anastomosis, Surgical / Q000009:adverse effects; D000818:Animals; D017536:Carotid Artery, Common / Q000166:cytology* / Q000637:transplantation*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D058426:Neointima / Q000473:pathology*; D014684:Venae Cavae / Q000637:transplantation*
references.citation: Vasc Cell. 2014 Mar 15;6(1):6
references.pmid: 24628920
references.citation: Circ Res. 2002 May 31;90(10):1128-34
references.pmid: 12039804
references.citation: Circulation. 1996 Oct 1;94(7):1655-64
references.pmid: 8840858
references.citation: Circulation. 1997 Jun 17;95(12):2684-93
references.pmid: 9193438
references.citation: Circulation. 1996 Jan 15;93(2):340-8
references.pmid: 8548908
references.citation: Curr Opin Nephrol Hypertens. 2004 May;13(3):279-84
references.pmid: 15073485
references.citation: J Am Coll Cardiol. 2004 Dec 7;44(11):2149-56
references.pmid: 15582312
references.citation: J Leukoc Biol. 2009 Nov;86(5):1111-8
references.pmid: 19581373
references.citation: Am J Pathol. 1998 Oct;153(4):1301-10
references.pmid: 9777962
references.citation: Cardiovasc Res. 2010 Dec 1;88(3):502-11
references.pmid: 20631156
references.citation: Dev Dyn. 1996 Mar;205(3):281-92
references.pmid: 8850564
references.citation: Development. 1994 Aug;120(8):2213-24
references.pmid: 7925022
references.citation: Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1744-51
references.pmid: 17541019
references.citation: Arterioscler Thromb Vasc Biol. 2010 Oct;30(10):1877-9
references.pmid: 20844267
references.citation: Cell Rep. 2012 Dec 27;2(6):1684-96
references.pmid: 23200853
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Jul;293(1):L1-8
references.pmid: 17384082
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1180-5
references.pmid: 15105282
references.citation: Circ Res. 2005 Apr 15;96(7):784-91
references.pmid: 15761195
references.citation: FASEB J. 1998 Sep;12(12):1135-42
references.pmid: 9737716
references.citation: Circulation. 1998 Mar 10;97(9):916-31
references.pmid: 9521341
references.citation: J Clin Invest. 2004 May;113(9):1258-65
references.pmid: 15124016
references.citation: Circ Res. 2011 Nov 11;109(11):1240-9
references.pmid: 21959220
references.citation: Circ Res. 2012 Jan 20;110(2):230-40
references.pmid: 22116816
references.citation: FASEB J. 2008 Feb;22(2):428-36
references.pmid: 17848623
references.citation: Genesis. 2007 Sep;45(9):593-605
references.pmid: 17868096
references.citation: J Clin Invest. 2008 Feb;118(2):515-25
references.pmid: 18188448
references.citation: Semin Cell Dev Biol. 2007 Feb;18(1):101-10
references.pmid: 17224285
references.citation: Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2579-81
references.pmid: 17110606
references.citation: Circulation. 2002 Oct 1;106(14):1834-9
references.pmid: 12356638
references.citation: Heart Lung Circ. 2002;11(3):182-8
references.pmid: 16352095
references.citation: Nat Commun. 2012 Jun 06;3:875
references.pmid: 22673902
references.citation: Am J Physiol Renal Physiol. 2007 Aug;293(2):F470-5
references.pmid: 17344190
references.citation: Dev Dyn. 2012 Feb;241(2):376-89
references.pmid: 22275227
references.citation: Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):257-66
references.pmid: 16322535
references.citation: Arterioscler Thromb Vasc Biol. 2011 Apr;31(4):808-13
references.pmid: 21233450
references.citation: Arterioscler Thromb Vasc Biol. 2012 Apr;32(4):955-61
references.pmid: 22308044
references.citation: Circulation. 1996 Jun 15;93(12):2178-87
references.pmid: 8925587
references.citation: Circ Res. 2005 Apr 29;96(8):904-12
references.pmid: 15790953
references.citation: Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):470-6
references.pmid: 14726410
references.citation: Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2696-702
references.pmid: 17008593