α ₂ (VIII) Collagen Substrata Enhance Endothelial Cell Retention Under Acute Shear Stress Flow via an α ₂ β ₁ Integrin–Dependent Mechanism

Abstract

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/cm 2 . ␣ 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 -␤ 1 (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/cm 2 , 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 (PϽ0.05) after 24 hours' implantation in the caprine carotid artery. Conclusions-These

Adhesion mechanisms of the mussel foot proteins mfp-1 and mfp-3

“…There are two possible explanations for this: shear-dependent conformational change and degradation. Shear-dependent conformational changes in integrin improve its binding to collagen (31), and the shear induced degradation of biopolymers into smaller fragments is well known, for example, shear fragmentation of DNA (32). Together, the results suggest that mfp-1 behaves as a protective coating and that mfp-3 is the real adhesive protein, acting like a ''glue'' for the mussels' binding onto surfaces.…”

Concise Review: Patency of Small-Diameter Tissue-Engineered Vascular Grafts: A Meta-Analysis of Preclinical Trials

“…S1). Exclusion of duplicates and then systematic screening of title and abstract using the Covidence platform revealed 321 studies, which was finally limited by thorough text reading to 68 studies based on inclusion criteria . These studies represented a total of 873 grafts: 258 occluded and 615 patent grafts at the end of the evaluation period.…”

Collagens in the progression and complications of atherosclerosis

“…A recent paper reports that type VIII collagen also mediates endothelial cell adhesion and spreading, and that adhesion of endothelial cells is accomplished via α 2 β 1 integrin binding to the amino acid sequence GLOGER located in the α 2 chain of type VIII collagen. 44 Given its important role in promoting migration, and increased expression after vascular injury, experiments are currently in progress studying the neointimal hyperplastic response in the injured arteries of the type VIII collagen-null mouse.…”