title: In vitro Study of a Novel Stent Coating Using Modified CD39 Messenger RNA to Potentially Reduce Stent Angioplasty-Associated Complications.
abstract: BACKGROUND
  Stent angioplasty provides a minimally invasive treatment for atherosclerotic vessels. However, no treatment option for atherosclerosis-associated endothelial dysfunction, which is accompanied by a loss of CD39, is available, and hence, adverse effects like thromboembolism and restenosis may occur. Messenger RNA (mRNA)-based therapy represents a novel strategy, whereby de novo synthesis of a desired protein is achieved after delivery of a modified mRNA to the target cells.
  
  
  RESULTS
  Our study aimed to develop an innovative bioactive stent coating that induces overexpression of CD39 in the atherosclerotic vessel. Therefore, a modified CD39-encoding mRNA was produced by in vitro transcription. Different endothelial cells (ECs) were transfected with the mRNA, and CD39 expression and functionality were analyzed using various assays. Furthermore, CD39 mRNA was immobilized using poly(lactic-co-glycolic-acid) (PLGA), and the transfection efficiency in ECs was analyzed. Our data show that ECs successfully translate in vitro-generated CD39 mRNA after transfection. The overexpressed CD39 protein is highly functional in hydrolyzing ADP and in preventing platelet activation. Furthermore, PLGA-immobilized CD39 mRNA can be delivered to ECs without losing its functionality.
  
  
  CONCLUSIONS
  In summary, we present a novel and promising concept for a stent coating for the treatment of atherosclerotic blood vessels, whereby patients could be protected against angioplasty-associated complications.
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Meike-Kristin
authors.initials: MK
authors.lastname: Abraham
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nolte
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Reus
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Behring
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Diane
authors.initials: D
authors.lastname: Zengerle
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Meltem
authors.initials: M
authors.lastname: Avci-Adali
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Jan David
authors.initials: JD
authors.lastname: Hohmann
authors.affiliation: Atherothrombosis and Vascular Biology, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schlensak
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Wendel
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Teubingen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Krajewski
mesh_terms: D017130:Angioplasty / Q000009:adverse effects / Q000379:methods*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001081:Apyrase / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000601:surgery*; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D012333:RNA, Messenger / Q000627:therapeutic use*; D015607:Stents / Q000009:adverse effects*; D013552:Swine
chemical_list: D015703:Antigens, CD; D012333:RNA, Messenger; D001081:Apyrase; C067869:CD39 antigen