Abstract

Progressive anastomotic stenosis is a significant cause of failure of small diameter synthetic grafts after arterial reconstruction. The mechanisms by which stenosis develops are not known but may relate to abnormal proliferation of vascular smooth muscle cells. The objective of this proposal is to define the role of endothelial (EC) and smooth muscle (SMC) proliferation in the formation of anastomotic stenoses in a baboon model of graft failure. In particular we shall investigate the possibility that this process is the result of: 1) initial SMC and EC migration and proliferation to cover the luminal surface of the graft; 2) persistent intimal SMKC proliferation at the anastomosis resulting in graft stenosis; 3) recurrent endothelia injury in regions of established anastomotic stenosis leading to accumulation of thrombus and accelerated SMC growth. The proposed studies will utilize baboon models of graft failure and arterial stenosis, light and electron microscopy, autoradiography, morphometry, and immunohistochemistry.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030946-03
Application #
3341962
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1983-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Sobel, Michael; Kikuchi, Shinsuke; Chen, Lihua et al. (2018) Clinical factors that influence the cellular responses of saphenous veins used for arterial bypass. J Vasc Surg 68:165S-176S.e6
Kikuchi, Shinsuke; Chen, Lihua; Xiong, Kevin et al. (2018) Smooth muscle cells of human veins show an increased response to injury at valve sites. J Vasc Surg 67:1556-1570.e9
Kenagy, Richard D; Kikuchi, Shinsuke; Evanko, Steve P et al. (2018) Versican is differentially regulated in the adventitial and medial layers of human vein grafts. PLoS One 13:e0204045
Kenagy, Richard D; Kikuchi, Shinsuke; Chen, Lihua et al. (2018) A single nucleotide polymorphism of cyclin-dependent kinase inhibitor 1B (p27Kip1) associated with human vein graft failure affects growth of human venous adventitial cells but not smooth muscle cells. J Vasc Surg 67:309-317.e7
Kikuchi, Shinsuke; Kenagy, Richard D; Gao, Lu et al. (2016) Surgical marking pen dye inhibits saphenous vein cell proliferation and migration in saphenous vein graft tissue. J Vasc Surg 63:1044-50
Kenagy, Richard D; Civelek, Mete; Kikuchi, Shinsuke et al. (2016) Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency. J Vasc Surg 64:202-209.e6
Siew, Edward D; Himmelfarb, Jonathan (2013) The inexorable rise of AKI: can we bend the growth curve? J Am Soc Nephrol 24:3-5
Sobel, Michael; Moreno, Katherine I; Yagi, Mayumi et al. (2013) Low levels of a natural IgM antibody are associated with vein graft stenosis and failure. J Vasc Surg 58:997-1005.e1-2
Conte, Michael S; Owens, Christopher D; Belkin, Michael et al. (2013) A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts. J Vasc Surg 57:1179-85.e1-2
Braun, Kathleen R; DeWispelaere, Allison M; Bressler, Steven L et al. (2012) Inhibition of PDGF-B induction and cell growth by syndecan-1 involves the ubiquitin and SUMO-1 ligase, Topors. PLoS One 7:e43701

Showing the most recent 10 out of 78 publications