title: Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction.
abstract: BACKGROUND
  Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries.
  
  
  OBJECTIVE
  Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study.
  
  
  RESULTS
  AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG.
  
  
  CONCLUSIONS
  These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.
authors.affiliation: Clinic of Internal Medicine I, Department of Cardiology, University Hospital Jena, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lichtenauer
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.forename: Gregor
authors.initials: G
authors.lastname: Werba
authors.forename: Lucian
authors.initials: L
authors.lastname: Beer
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
authors.forename: Andrea
authors.initials: A
authors.lastname: Baumgartner
authors.forename: Matthias
authors.initials: M
authors.lastname: Hasun
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nickl
authors.forename: Andreas
authors.initials: A
authors.lastname: Mitterbauer
authors.forename: Matthias
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
authors.forename: Bruno Karl
authors.initials: BK
authors.lastname: Podesser
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D011817:Rabbits; D051381:Rats; D060168:Thymocytes / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000961:Antilymphocyte Serum; D002316:Cardiotonic Agents; D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators; D016159:Tumor Suppressor Protein p53