This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 114/8/820    most recent CIRCULATIONAHA.106.635292v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Turner, N. J. Articles by Canfield, A. E. Search for Related Content PubMed PubMed Citation Articles by Turner, N. J. Articles by Canfield, A. E. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Related Collections Cell biology/structural biology Endothelium/vascular type/nitric oxide Other Vascular biology

(Circulation. 2006;114:820-829.)
© 2006 American Heart Association, Inc.

Molecular Cardiology

₂(VIII) Collagen Substrata Enhance Endothelial Cell Retention Under Acute Shear Stress Flow via an ₂ß₁ Integrin–Dependent Mechanism

An In Vitro and In Vivo Study

Neill J. Turner, PhD; Michael O. Murphy, MRCS; Cay M. Kielty, PhD; C. Adrian Shuttleworth, PhD; Richard A. Black, PhD; Martin J. Humphries, PhD; Michael G. Walker, ChM, FRCS; Ann E. Canfield, PhD

From UK Centre for Tissue Engineering (N.J.T., M.O.M., C.M.K., R.A.B., M.G.W., A.E.C.), Universities of Manchester (N.J.T., M.O.M., C.M.K., M.G.W., A.E.C.) and Liverpool (R.A.B.); Department of Vascular Surgery (N.J.T., M.O.M., M.G.W.), Manchester Royal Infirmary; Wellcome Trust Centre for Cell Matrix Research (C.M.K., C.A.S., M.J.H., A.E.C.), University of Manchester; and Faculty of Medicine and Human Sciences (A.E.C.), University of Manchester; Manchester, United Kingdom.

Correspondence to Dr Ann Canfield, Michael Smith Building, Oxford Rd, University of Manchester, Manchester, M13 9PT, United Kingdom. E-mail ann.canfield{at}manchester.ac.uk

Received October 14, 2005; de novo received April 21, 2006; revision received June 8, 2006; accepted June 22, 2006.

Background— Essential to tissue-engineered vascular grafts is the formation of a functional endothelial monolayer capable of resisting the forces of blood flow. This study targeted ₂(VIII) collagen, a major component of the subendothelial matrix, and examined the ability of and mechanisms by which endothelial cells attach to this collagen under static and dynamic conditions both in vitro and in vivo.

Methods and Results— Attachment of human endothelial cells to recombinant ₂(VIII) collagen was assessed in vitro under static and shear conditions of up to 100 dyne/cm². ₂(VIII) collagen supported endothelial cell attachment in a dose-dependent manner, with an 18-fold higher affinity for endothelial cells compared with fibronectin. Cell attachment was significantly inhibited by function-blocking anti-₂ (56%) and -ß₁ (98%) integrin antibodies but was not RGD dependent. Under flow, endothelial cells were retained at significantly higher levels on ₂(VIII) collagen (53% and 51%) than either fibronectin (23% and 16%) or glass substrata (7% and 1%) at shear rates of 30 and 60 dyne/cm², respectively. In vivo studies, using endothelialized polyurethane grafts, demonstrated significantly higher cell retention rates to ₂(VIII) collagen-coated than to fibronectin-coated prostheses in the midgraft area (P<0.05) after 24 hours’ implantation in the caprine carotid artery.

Conclusions— These studies demonstrate that ₂(VIII) collagen has the potential to improve both initial cell attachment and retention of endothelial cells on vascular grafts in vivo, which opens new avenues of research into the development of single-stage endothelialized prostheses and the next generation of tissue-engineered vascular grafts.

---

 

CLINICAL PERSPECTIVE

This article has been cited by other articles:

				E. Adiguzel, P. J Ahmad, C. Franco, and M. P Bendeck Collagens in the progression and complications of atherosclerosis Vascular Medicine, February 1, 2009; 14(1): 73 - 89. [Abstract] [PDF]

				Q. Lin, D. Gourdon, C. Sun, N. Holten-Andersen, T. H. Anderson, J. H. Waite, and J. N. Israelachvili Adhesion mechanisms of the mussel foot proteins mfp-1 and mfp-3 PNAS, March 6, 2007; 104(10): 3782 - 3786. [Abstract] [Full Text] [PDF]