title: Liposomal delivery of heat-shock protein 72 into the heart prevents endotoxin-induced myocardial contractile dysfunction.
abstract: BACKGROUND
  The purposes of this study were to (1) determine whether functional heat-shock protein 72 (HSP-72) may be delivered into the heart, (2) determine whether HSP-72 itself is protective against endotoxin (lipopolysaccharide [LPS]-induced cardiodepression, and (3) compare relative protection and time courses required for protection for thermally induced HSP-72 versus liposomally introduced HSP-72.
  
  
  METHODS
  HSP-72 was introduced (liposomal HSP-72) or induced (heat shock, 42 degrees C x 15 minutes, 24 hours before) in rat heart before LPS administration (0.5 mg/kg intraperitoneal or ex vivo coronary infusion). Western blot analysis for HSP-72 was used to confirm its expression. Left ventricular developed pressure (Langendorff) was used as an index of cardiac function.
  
  
  RESULTS
  Direct intracoronary perfusion of liposomal HSP-72 delivered functioning HSP-72 into the myocardium. LPS induced cardiodepression; however, heat shock pretreatment abolished LPS-induced contractile dysfunction. A direct connection was found between HSP-72 and protection derived from liposomal transfer experiments that similarly reduced LPS-induced cardiodepression.
  
  
  CONCLUSIONS
  (1) HSP-72 prevents LPS-induced myocardial contractile dysfunction, (2) liposomal transfer of HSP-72 into the myocardium provides the first direct mechanistic connection between myocardial HSP-72 and protection against LPS, (3) HSP-72 induction requires 24 hours and liposomal transfer of HSP-72 requires 90 minutes, and (4) HSP-72 may offer a clinically acceptable means of protecting the heart.
authors.affiliation: Department of Surgery, University of Colorado Health Sciences Center, Denver, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.forename: B D
authors.initials: BD
authors.lastname: Shames
authors.forename: B
authors.initials: B
authors.lastname: Pomerantz
authors.forename: K K
authors.initials: KK
authors.lastname: Donnahoo
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000818:Animals; D004337:Drug Carriers; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000008:administration & dosage* / Q000096:biosynthesis; D006358:Hot Temperature; D008070:Lipopolysaccharides / Q000633:toxicity*; D008081:Liposomes; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004337:Drug Carriers; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D008081:Liposomes