title: Effect of vascular stent alloys on expression of cellular adhesion molecules by endothelial cells.
abstract: OBJECTIVE
  Nickel and cobalt ions activate ICAM1 expression on endothelial cells and keratinocytes. Furthermore, these ions are released in vitro and in vivo from the types of alloys used for vascular stents, but the full biological consequences of this release is not known. In the current study, we determined if release of elements from vascular stent alloys that contained nickel and cobalt was sufficient to activate expression of key cellular adhesion molecules (CAMs) by endothelial cells. Expression of these CAMs is a critical step in the long-term inflammatory response to stent materials and possibly to in-stent restenonsis.
  
  
  METHODS
  Stainless steel, NiTi, CoCrNi, and NiCr alloys were placed in direct contact with primary human microvascular endothelial cells for 72 hours after preparation at three roughnesses (120, 320, and 1200 grit). Expression of three CAMs--ICAM1, VCAM1, and e-selectin--was assessed using a modified ELISA procedure. Cytotoxicity of the alloys was assessed by measuring succinate dehydrogenase (SDH) activity and total protein content of the cells, and nickel release was measured by atomic absorption spectroscopy.
  
  
  RESULTS
  None of the alloys suppressed SDH activity or total cellular protein significantly at any surface roughness, indicating little or no cytotoxicity. Ni release was measurable from all alloys, was greatest from the rougher surfaces, and was significantly different for the different alloy types. NiTi alloys exhibited the lowest nickel release. However, none of the alloys activated expression of the CAMs, regardless of surface roughness or nickel release level. Supplemental experiments using nickel ions alone confirmed that ICAM1 was inducible on the endothelial cells by Ni(II) concentrations above 100 microM.
  
  
  CONCLUSIONS
  In this in vitro system, nickel or other elemental release from several common types of stent alloys was not sufficient to activate expression of CAMs on endothelial surfaces. Although these results indicate a low risk for direct activation of endothelial cells by ions released from stent alloys, other mechanisms, such as modulation of CAM expression by monocytes or smooth muscle cells, must be considered before ion-mediated influence on CAM expression can be dismissed.
authors.affiliation: Medical College of Georgia, Augusta, Georgia 30912-1100, USA. rmesser@mcg.edu
authors.forename: Regina L W
authors.initials: RL
authors.lastname: Messer
authors.forename: John C
authors.initials: JC
authors.lastname: Wataha
authors.forename: Jill B
authors.initials: JB
authors.lastname: Lewis
authors.forename: Petra E
authors.initials: PE
authors.lastname: Lockwood
authors.forename: Gretchen B
authors.initials: GB
authors.lastname: Caughman
authors.forename: Wu-Yan
authors.initials: WY
authors.lastname: Tseng
mesh_terms: D000497:Alloys / Q000633:toxicity*; D000704:Analysis of Variance; D001672:Biocompatible Materials; D001807:Blood Vessel Prosthesis; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*; D008422:Materials Testing; D009532:Nickel / Q000633:toxicity; D012680:Sensitivity and Specificity; D013054:Spectrophotometry, Atomic; D013385:Succinate Dehydrogenase / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*
chemical_list: D000497:Alloys; D001672:Biocompatible Materials; D019010:Vascular Cell Adhesion Molecule-1; D002857:Chromium; D018799:Intercellular Adhesion Molecule-1; D009532:Nickel; D013385:Succinate Dehydrogenase