Abstract 11660: A Mixture of Fibronectin, Fibrinogen and Tropoelastin is Able to Inhibit Smooth Muscle Cell Migration and to Promote Reendothelialization in vitro
Reendothelialization of the stent surface after PCI is known to be an important determinant of clinical outcome. The effect of different biological stent coatings on reendothelialization and smooth muscle cell activation are relatively unexplored. We compared the effects of fibronectin (FN), fibrinogen (Fg) and tropoelastin (tropo) coatings on endothelial (HUVEC) and smooth muscle cell (VSMC) characteristics. Umbilical cord arterial segments were plated on coated surfaces and the area around the segments covered with VSMCs was measured after 12 days to assess VSMC proliferation and migration. mRNA was isolated from HUVEC and VSMC cultured on the different coatings for 24 hours and QPCRs were performed for gene analysis. Tissue factor (TF) expression was measured by factor X activation to factor Xa, which was quantified with a chromogenic substrate. There was a clear difference in VSMC covered surface among different coatings: 31.2±4.0mm2 on FN, 1.6±0.3mm2 on tropo and 8.1±1.5mm2 on a mixture of FN/Fg/tropo. HUVEC migration was unaffected by the different coatings. Culturing HUVEC on tropo resulted in increased mRNA expression of VCAM-1 (13.1±4.4pg/ml), ICAM-1 (5.1±1.3pg/ml) and IL-8 (11.6±3.1pg/ml) compared to FN (0.7±0.2pg/ml, 0.8±0.2pg/ml, 2.3±0.5pg/ml respectively) while this increased gene expression was not found in the mixture of FN/Fg/tropo. No significant differences in VCAM-1, ICAM-1 and IL-8 mRNA expression were found in VSMC. Finally, we observed an increased TF activity of HUVEC cultured on tropo (511.6 ± 26.7%) compared to FN while cells cultured on the mixture FN/Fg/tropo did not have increased TF activity (76.3 ± 25.0%). These results indicate that a tropoelastin surface inhibits VSMC migration but leads to an increase in inflammatory and procoagulant marker on endothelial cells. In a mixture of FN/Fg/tropo, the inflammatory effects of tropo are compensated while VSMC activation and migration is still inhibited. Coating a mixture FN/Fg/tropo on a stent might combine the favorable reendothelialization effects, while restenosis and procoagulant activity will be controlled.
- © 2011 by American Heart Association, Inc.