title: Tissue kallikrein deficiency aggravates cardiac remodelling and decreases survival after myocardial infarction in mice.
abstract: BACKGROUND
  Tissue kallikrein (TK) is a major kinin-releasing enzyme present in arteries. TK is involved in cardioprotection in the setting of acute myocardial ischaemia but its role in post-ischaemic heart failure (HF), a major cause of delayed mortality after myocardial infarction (MI), is unknown.
  
  
  OBJECTIVE
  To determine whether TK deficiency in the mouse influences survival and cardiac remodelling after MI.
  
  
  METHODS
  MI was induced in 10 week-old male TK-deficient mice and wild-type littermates. Survival was assessed up to 14 months. Cardiac morphological and functional parameters were serially measured by echocardiography. In another experiment, myocardial capillary density and NOS content were evaluated at 3 months.
  
  
  RESULTS
  Infarct size was similar in both genotypes. MI resulted in severe cardiac dysfunction. Up to 12 months after MI, TK(-/-) mice displayed an increased mortality rate (P<0.05, relative risk of death=3.41) and aggravation of left ventricular hypertrophy and dilatation by comparison with TK(+/+) (+18% and +27% respectively, both P<0.05). NOS1 and NOS3 were abnormally regulated in the heart of TK(-/-) mice after MI.
  
  
  CONCLUSIONS
  TK exerts a protective role in HF in mice. Coronary effects are probably involved. As partial genetic deficiency in TK activity occurs in humans, TK-deficient subjects may be at increased risk of mortality in HF.
authors.affiliation: INSERM U 652/872, CRC, IFR 58, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pons
authors.forename: Violaine
authors.initials: V
authors.lastname: Griol-Charhbili
authors.forename: Christophe
authors.initials: C
authors.lastname: Heymes
authors.forename: Paul
authors.initials: P
authors.lastname: Fornes
authors.forename: Didier
authors.initials: D
authors.lastname: Heudes
authors.forename: Albert
authors.initials: A
authors.lastname: Hagege
authors.forename: Xavier
authors.initials: X
authors.lastname: Loyer
authors.forename: Pierre
authors.initials: P
authors.lastname: Meneton
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Giudicelli
authors.forename: Jane-Lise
authors.initials: JL
authors.lastname: Samuel
authors.forename: François
authors.initials: F
authors.lastname: Alhenc-Gelas
authors.forename: Christine
authors.initials: C
authors.lastname: Richer
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D004452:Echocardiography; D007705:Kinins / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009929:Organ Size; D013318:Stroke Volume / Q000502:physiology; D015996:Survival Rate; D020840:Tissue Kallikreins / Q000172:deficiency / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D007705:Kinins; D019001:Nitric Oxide Synthase; D020840:Tissue Kallikreins