Novel approach for endothelializing vascular devices: understanding and exploiting elastin-endothelial interactions.

Elastin is an essential component of arteries which provides structural integrity and instructs smooth muscle cells to adopt a quiescent state. Despite interaction of endothelial cells with elastin in the internal elastic lamina, the potential for exploiting this interaction therapeutically has not been explored in detail. In this study, we show that tropoelastin (a precursor of elastin) stimulates endothelial cell migration and adhesion more than smooth muscle cells. The biological activity of tropoelastin on endothelial cells is contained in the VGVAPG domain and in the carboxy-terminal 17-amino acids. We show that the effects of the carboxy-terminal 17 amino acids, but not those of VGVAPG, are mediated by integrin α(V)ß(3). We demonstrate that tropoelastin covalently linked to stainless steel disks promotes adhesion of endothelial progenitor cells and endothelial cells to the metal surfaces. The adherent cells on the tropoelastin-coated metal surfaces form monolayers that can withstand and respond to arterial shear stress. Because of the unique effects of tropoelastin on endothelial and smooth muscle cells, coating intravascular devices with tropoelastin may stimulate their endothelialization, inhibit smooth muscle hyperplasia, and improve device performance.

Anti-CD34 antibodies immobilized on the surface of sirolimus-eluting stents enhance stent endothelialization.

OBJECTIVES: In this study, we hypothesized that an antihuman-CD34 antibody immobilized on the surface of commercially available sirolimus-eluting stents (SES) could enhance re-endothelialization compared with SES alone. BACKGROUND: Previous experience with antihuman-CD34 antibody surface modified Genous stents (GS) (OrbusNeich Medical, Fort Lauderdale, Florida) has shown enhanced stent endothelialization in vivo. METHODS: In the phase 1 study, stents were deployed in 21 pig coronary arteries for single stenting (9 vessels: 3 GS, 3 SES, and 3 bare-metal stents) and overlapping stenting with various combinations (12 vessels: 4 GS+GS, 4 SES+SES, and 4 GS+SES) and harvested at 14 days for scanning electron and confocal microscopy. In phase 2, immobilized anti-CD34 antibody coating was applied on commercially available SES (SES-anti-CD34, n = 7) and compared with GS (n = 8) and SES (n = 7) and examined at 3 and 14 days by scanning electron/confocal microscopy analysis. RESULTS: In phase 1, single stent implantation showed greatest endothelialization in GS (99%) and in bare-metal stent (99%) compared with SES (55%, p = 0.048). In overlapping stents, endothelialization at the overlapping zone was significantly greater in GS+GS (95 +/- 6%) and GS+SES (79 +/- 5%) compared with the SES+SES (36 +/- 14%) group (p = 0.007). In phase 2, SES-anti-CD34 resulted in increased endothelialization compared with SES alone at 3 days (SES-anti-CD34 36 +/- 26%; SES 7 +/- 3%; and GS 76 +/- 8%; p = 0.01), and 14 days (SES-anti-CD34 82 +/- 8%; SES 53 +/- 20%; and GS 98 +/- 2%; p = 0.009). CONCLUSIONS: Immobilization of anti-CD34 antibody on SES enhances endothelialization and may potentially be an effective therapeutic alternative to improve currently available drug-eluting stents.