title: Thymosin β4 attenuates microcirculatory and hemodynamic destabilization in sepsis.
abstract: OBJECTIVE
  The actin polymerization regulator Thymosin β4 (Tβ4) has been shown to be involved in angiogenesis, wound healing, cell survival and anti-inflammatory responses. We have previously shown that Tβ4 is capable of recruiting pericytes, thus stabilizing the endothelial barrier function. Here, we analyzed whether treatment with Tβ4 is able to reduce the pericytes loss in lipopolysaccharides (LPS)-induced sepsis and to improve the hemodynamic function and survival in C57BL/6 mice.
  
  
  METHODS
  Fourteen days before LPS injection, the mice were injected with an adeno-associated virus carrying the Tβ4 (rAAV.Tβ4) or LacZ gene (rAAV.LacZ). A sepsis-severity score was assessed, and non-invasive hemodynamic and permeability measurements were performed. Heart and muscle samples were analyzed for PECAM-1(+) capillaries and NG2(+)pericytes.
  
  
  RESULTS
  At 36 h, there was a decrease of sepsis severity score in rAAV.Tβ4-treated animals as compared to rAAV.LacZ-treated control. rAAV.Tβ4-treated animals displayed lower perivascular leakage and higher blood pressure compared to control. Of note, the rAAV.Tβ4 group showed a higher pericyte count in heart and peripheral muscle samples. Finally, Tβ4-treatment reduced mortality compared to control.
  
  
  CONCLUSIONS
  The data indicate a preventive role of Tβ4 in septic hypercirculation and highlight Tβ4 as a potential therapeutic target in severe sepsis.
authors.affiliation: Klinikum der Universität München, Medizinische Klinik und Poliklinik I , Marchioninistr. 15, 81377 Munich , Germany +49 89 44007 3075 ; +49 89 44007 6075 ; Dario.bongionvanni@med.uni-muenchen.de.
authors.forename: Dario
authors.initials: D
authors.lastname: Bongiovanni
authors.forename: Tilman
authors.initials: T
authors.lastname: Ziegler
authors.forename: Sascha
authors.initials: S
authors.lastname: D'Almeida
authors.forename: Tianqiong
authors.initials: T
authors.lastname: Zhang
authors.forename: Judy K M
authors.initials: JK
authors.lastname: Ng
authors.forename: Steffen
authors.initials: S
authors.lastname: Dietzel
authors.forename: Rabea
authors.initials: R
authors.lastname: Hinkel
authors.forename: Christian
authors.initials: C
authors.lastname: Kupatt
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D000229:Dependovirus; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D020286:Pericytes / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology / Q000628:therapy*; D013947:Thymosin / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014945:Wound Healing / Q000235:genetics; D000099201:Thymosin beta(4)
chemical_list: D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: pericytes; septic shock; severe sepsis; thymosin β4