Tissue kallikrein deficiency aggravates cardiac remodelling and decreases survival after myocardial infarction in mice.
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.
Pons
Sandrine
S
INSERM U 652/872, CRC, IFR 58, Paris, France.
Griol-Charhbili
Violaine
V
Heymes
Christophe
C
Fornes
Paul
P
Heudes
Didier
D
Hagege
Albert
A
Loyer
Xavier
X
Meneton
Pierre
P
Giudicelli
Jean-François
JF
Samuel
Jane-Lise
JL
Alhenc-Gelas
François
F
Richer
Christine
C
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*
D007705:Kinins; D019001:Nitric Oxide Synthase; D020840:Tissue Kallikreins