A fibronectin-fibrinogen-tropoelastin coating reduces smooth muscle cell growth but improves endothelial cell function
نویسندگان
چکیده
Reendothelialization of the stent surface after percutaneous coronary intervention (PCI) is known to be an important determinant of clinical outcome. We compared the effects of biological stent coatings, fibronectin, fibrinogen and tropoelastin, on human umbilical vein endothelial cell (HUVEC) and vascular smooth muscle cell (VSMC) characteristics. Umbilical cord arterial segments were cultured on coated surfaces and VSMC outgrowth (indicating proliferation and migration) was measured after 12 days. mRNA was isolated from HUVEC and VSMC cultured on these coatings and gene expression was profiled by QPCR. Procoagulant properties of HUVEC were determined by an indirect chromogenic assay which detects tissue factor activity. The varying stent coatings influence VSMC outgrowth: 31.2 ± 4.0 mm(2) on fibronectin, 1.6 ± 0.3 mm(2) on tropoelastin and 8.1 ± 1.5 mm(2) on a mixture of fibronectin/fibrinogen/tropoelastin, although HUVEC migration remains unaffected. Culturing HUVEC on tropoelastin induces increased expression of VCAM-1 (13.1 ± 4.4 pg/ml), ICAM-1 (5.1 ± 1.3 pg/ml) and IL-8 (11.6 ± 3.1 pg/ml) compared to fibronectin (0.7 ± 0.2, 0.8 ± 0.2, 2.3 ± 0.5 pg/ml, respectively), although expression levels on fibronectin/fibrinogen/tropoelastin remain unaltered. No significant differences in VCAM-1, ICAM-1 and IL-8 mRNA expression are found in VSMC. Finally, HUVEC cultured on tropoelastin display a fivefold increased tissue factor activity (511.6 ± 26.7%), compared to cells cultured on fibronectin (100 ± 3.9%) or fibronectin/fibrinogen/tropoelastin (76.3 ± 25.0%). These results indicate that tropoelastin inhibits VSMC migration but leads to increased inflammatory and procoagulant markers on endothelial cells. Fibronectin/fibrinogen/tropoelastin inhibits VSMCs while compensating the inflammatory and procoagulant effects. These data suggest that coating a mixture of fibronectin/fibrinogen/tropoelastin on a stent may promote reendothelialization, while keeping unfavourable processes such as restenosis and procoagulant activity limited.
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