Absence of NF-kappaB subunit p50 improves heart failure after myocardial infarction.
BACKGROUND
NF kappa B (NF-kappaB) is a ubiquitous transcription factor activated by various stimuli implicated in heart failure progression including reactive oxygen species (ROS), hypoxia, and inflammatory cytokines. Although NF-kappaB is involved in ischemic preconditioning, unstable angina pectoris, and atherogenesis, its role in heart failure has not been determined. Therefore, we investigated left ventricular remodeling in mice with a targeted deletion of the NF-kappaB subunit p50/NF-kappaB1 after myocardial infarction.


RESULTS
p50 knockout (KO) and wild-type (WT) animals underwent coronary artery ligation. Transthoracic echocardiography was performed at days 0, 21, and 56 at midpapillary levels. Early mortality was significantly lower in KO than in WT animals. Moreover, p50 KOs exhibited significantly reduced ventricular dilatation over 8 wk compared to WT controls (end-systolic diameters by transthoracic echocardiography, WT vs. KO, 0.55+/-0.04 vs. 0.34+/-0.03 cm) and preserved left ventricular contractility. Collagen content and matrixmetalloproteinase (MMP) -9 expression were significantly lower in KO mice after myocardial infarction and may account for improved left ventricular remodeling.


CONCLUSIONS
Absence of the NF-kappaB subunit p50 improves early survival and reduces left ventricular dilatation after myocardial infarction. NF-kappaB might therefore be an attractive target to treat heart failure.
Frantz
Stefan
S
Medizinische Klinik und Poliklinik I, Herzkreislauf-Zentrum, Universität Würzburg, Germany. frantz_s@medizin.uni-wuerzburg.de
Hu
Kai
K
Bayer
Barbara
B
Gerondakis
Steve
S
Strotmann
Jörg
J
Adamek
Anna
A
Ertl
Georg
G
Bauersachs
Johann
J
D000818:Animals; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels; D003971:Diastole; D004195:Disease Models, Animal; D004452:Echocardiography; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007249:Inflammation; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology*; D052002:NF-kappa B p50 Subunit / Q000172:deficiency*; D009929:Organ Size; D016019:Survival Analysis; D013599:Systole; D020257:Ventricular Remodeling / Q000502:physiology
D052002:NF-kappa B p50 Subunit; D003094:Collagen