The role of endothelial cell attachment to elastic fibre molecules in the enhancement of monolayer formation and retention, and the inhibition of smooth muscle cell recruitment.
The endothelium is an essential modulator of vascular tone and thrombogenicity and a critical barrier between the vessel wall and blood components. In tissue-engineered small-diameter vascular constructs, endothelial cell detachment in flow can lead to thrombosis and graft failure. The subendothelial extracellular matrix provides stable endothelial cell anchorage through interactions with cell surface receptors, and influences the proliferation, migration, and survival of both endothelial cells and smooth muscle cells. We have tested the hypothesis that these desired physiological characteristics can be conferred by surface coatings of natural vascular matrix components, focusing on the elastic fiber molecules, fibrillin-1, fibulin-5 and tropoelastin. On fibrillin-1 or fibulin-5-coated surfaces, endothelial cells exhibited strong integrin-mediated attachment in static conditions (82% and 76% attachment, respectively) and flow conditions (67% and 78% cell retention on fibrillin-1 or fibulin-5, respectively, at 25 dynes/cm2), confluent monolayer formation, and stable functional characteristics. Adhesion to these two molecules also strongly inhibited smooth muscle cell migration to the endothelial monolayer. In contrast, on elastin, endothelial cells attached poorly, did not spread, and had markedly impaired functional properties. Thus, fibrillin-1 and fibulin-5, but not elastin, can be exploited to enhance endothelial stability, and to inhibit SMC migration within vascular graft scaffolds. These findings have important implications for the design of vascular graft scaffolds, the clinical performance of which may be enhanced by exploiting natural cell-matrix biology to regulate cell attachment and function.
Williamson
Matthew R
MR
Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK.
Shuttleworth
Adrian
A
Canfield
Ann E
AE
Black
Richard A
RA
Kielty
Cay M
CM
D002448:Cell Adhesion / Q000502:physiology; D002464:Cell Migration Inhibition / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004548:Elasticity; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D054392:Adipokines
D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C492373:FBLN5 protein, human; C000605722:FBN1 protein, human; D054392:Adipokines