title: Endogenous C1-inhibitor production and expression in the heart after acute myocardial infarction.
abstract: BACKGROUND
  Complement activation contributes significantly to inflammation-related damage in the heart after acute myocardial infarction. Knowledge on factors that regulate postinfraction complement activation is incomplete however. In this study, we investigated whether endogenous C1-inhibitor, a well-known inhibitor of complement activation, is expressed in the heart after acute myocardial infarction.
  
  
  METHODS
  C1-inhibitor and complement activation products C3d and C4d were analyzed immunohistochemically in the hearts of patients who died at different time intervals after acute myocardial infarction (n=28) and of control patients (n=8). To determine putative local C1-inhibitor production, cardiac transcript levels of the C1-inhibitor-encoding gene serping1 were determined in rats after induction of acute myocardial infarction (microarray). Additionally, C1-inhibitor expression was analyzed (fluorescence microscopy) in human endothelial cells and rat cardiomyoblasts in vitro.
  
  
  RESULTS
  C1-inhibitor was found predominantly in and on jeopardized cardiomyocytes in necrotic infarct cores between 12h and 5days old. C1-inhibitor protein expression coincided in time and colocalized with C3d and C4d. In the rat heart, serping1 transcript levels were increased from 2h up until 7days after acute myocardial infarction. Both endothelial cells and cardiomyoblasts showed increased intracellular expression of C1-inhibitor in response to ischemia in vitro (n=4).
  
  
  CONCLUSIONS
  These observations suggest that endogenous C1-inhibitor is likely involved in the regulation of complement activity in the myocardium following acute myocardial infarction. Observations in rat and in vitro suggest that C1-inhibitor is produced locally in the heart after acute myocardial infarction.
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of Immunopathology, Sanquin Research, Postbus 9892, 1006 AN, Amsterdam, The Netherlands. Electronic address: r.emmens@vumc.nl.
authors.forename: Reindert W
authors.initials: RW
authors.lastname: Emmens
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: u.baylan@vumc.nl.
authors.forename: Umit
authors.initials: U
authors.lastname: Baylan
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Interuniversity Cardiology Institute of The Netherlands, Postbus 19258, 3501 DG, Utrecht, The Netherlands. Electronic address: ljm.juffermans@vumc.nl.
authors.forename: Lynda J M
authors.initials: LJ
authors.lastname: Juffermans
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: rashmi.v.karia@gmail.com.
authors.forename: Rashmi V
authors.initials: RV
authors.lastname: Karia
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: b.ylstra@vumc.nl.
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.affiliation: Department of Immunopathology, Sanquin Research, Postbus 9892, 1006 AN, Amsterdam, The Netherlands. Electronic address: d.wouters@sanquin.nl.
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.affiliation: Department of Immunopathology, Sanquin Research, Postbus 9892, 1006 AN, Amsterdam, The Netherlands; Department of Hematology, Academic Medical Center, Postbus 22660, 1100 AD, Amsterdam, The Netherlands. Electronic address: s.s.zeerleder@amc.uva.nl.
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.affiliation: Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of Internal Medicine, Medical Center Alkmaar, Postbus 501, 1800 AM, Alkmaar, The Netherlands. Electronic address: s.simsek@mca.nl.
authors.forename: Suat
authors.initials: S
authors.lastname: Simsek
authors.affiliation: Department of Immunopathology, Sanquin Research, Postbus 9892, 1006 AN, Amsterdam, The Netherlands. Electronic address: m.vanham@sanquin.nl.
authors.forename: Marieke
authors.initials: M
authors.lastname: van Ham
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of Cardiac Surgery, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: jwm.niessen@vumc.nl.
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. Electronic address: paj.krijnen@vumc.nl.
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
mesh_terms: D000818:Animals; D002460:Cell Line; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D050718:Complement C1 Inhibitor Protein; D015933:Complement C3d / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D032386:Myoblasts, Cardiac / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D010446:Peptide Fragments / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012189:Retrospective Studies; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; C469952:SERPING1 protein, human; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d
keywords: Acute myocardial infarction; C1-inhibitor; Complement; Ischemia