title: Origin of restenosis after drug-eluting stent implantation in hyperglycemia is inflammatory cells and thrombus.
abstract: OBJECTIVE
  The cellular and molecular mechanisms and safety after drug-eluting stent (DES) implantation in diabetic patients are still poorly understood; therefore, in this study, we evaluated the pathologic responses of the sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES) in a type I diabetes mellitus (DM) rat model.
  
  
  METHODS
  The type I DM rat model was manipulated by intra-peritoneal streptozotocin injection. Two weeks later, DES was implanted in the aorta of rats with hyperglycemia or not as a control. Four weeks after DES implantation, the stented aorta was isolated and histomorphometric analysis was performed.
  
  
  RESULTS
  On histomorphometric analysis, increased thrombus, inflammatory cell infiltration, and neointimal hyperplasia (NIH) without change of the smooth muscle cell number after DES implantation were observed in DM rats compared with non-DM (NDM) rats. Furthermore, delayed coverage of mature endothelial cells defined as a von Willebrand factor expression and increased immature endothelial cells as a c-kit expression after DES implantation were observed in DM rats compared with NDM rats. Increased fibrin deposition and decreased hyaluronic acid accumulation at NIH after DES implantation were also observed in DM rats compared with NDM rats.
  
  
  CONCLUSIONS
  In conclusion, the main mechanism of restenosis after DES implantation under hyperglycemic conditions was initial thrombus with changes of the extracellular matrix rather than SMC proliferation. These results provided a therapeutic clue for the selection of DES and application of combination therapy using anti-thrombotic and anti-inflammatory drugs in diabetic patients.
authors.affiliation: Stem Cell Research Center of Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kwon
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Ae Shin
authors.initials: AS
authors.lastname: Cho
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Seo Yeon
authors.initials: SY
authors.lastname: Jeong
authors.forename: Moon Hwa
authors.initials: MH
authors.lastname: Hong
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001011:Aorta / Q000473:pathology; D001835:Body Weight; D023903:Coronary Restenosis / Q000209:etiology / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy*; D007249:Inflammation / Q000209:etiology*; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology*
chemical_list: D000893:Anti-Inflammatory Agents; D005337:Fibrin; D006820:Hyaluronic Acid; D017239:Paclitaxel; D020123:Sirolimus