title: Transducible recombinant small heat shock-related protein, HSP20, inhibits vasospasm and platelet aggregation.
abstract: BACKGROUND
  Human saphenous vein (HSV) is the autologous conduit of choice for peripheral vascular reconstruction. Injury during harvest leads to vasospasm and a thrombogenic endoluminal surface. A proteomic transduction approach was developed to prevent vein graft vasospasm and thrombosis.
  
  
  METHODS
  Recombinant HSP20 protein linked to the TAT protein transduction domain was generated in a bacterial expression system (TAT-HSP20). The effect of this protein on the inhibition of smooth muscle contraction was determined using rings of rabbit aorta and HSV in a muscle bath. In addition, the effects of TAT-HSP20 on platelet aggregation were determined in vitro using human citrated whole blood.
  
  
  RESULTS
  Recombinant TAT-HSP20 inhibited norepinephrine-induced contraction of rabbit aortic and HSV segments. Similarly, TAT-HSP20 induced smooth muscle relaxation in HSV segments precontracted with norepinephrine. In human-citrated whole blood, platelet aggregation was significantly inhibited by TAT-HSP20 in a dose-dependent manner.
  
  
  CONCLUSIONS
  The results of this study demonstrate that recombinant TAT-HSP20 inhibits vascular smooth muscle contraction and platelet aggregation. This suggests that HSP20 may be an ideal effector molecule to target as a proteomic approach to enhance early vein graft patency rates by preventing acute vasospasm and thrombosis.
authors.affiliation: Department of Surgery, Mayo Clinic, Scottsdale, Ariz, USA.
authors.forename: Elisabeth C
authors.initials: EC
authors.lastname: McLemore
authors.forename: Deron J
authors.initials: DJ
authors.lastname: Tessier
authors.forename: C Robert
authors.initials: CR
authors.lastname: Flynn
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Furnish
authors.forename: Padmini
authors.initials: P
authors.lastname: Komalavilas
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Thresher
authors.forename: Lokesh
authors.initials: L
authors.lastname: Joshi
authors.forename: William M
authors.initials: WM
authors.lastname: Stone
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fowl
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Brophy
mesh_terms: D000818:Animals; D001011:Aorta; D001808:Blood Vessels / Q000187:drug effects*; D015696:Gene Products, tat / Q000235:genetics; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D011994:Recombinant Proteins; D012501:Saphenous Vein; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D015696:Gene Products, tat; D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D011994:Recombinant Proteins