NF-kappaB activation is required for the development of cardiac hypertrophy in vivo.
In the present study, we examined whether NF-kappaB activation is required for cardiac hypertrophy in vivo. Cardiac hypertrophy in rats was induced by aortic banding for 1, 3, and 5 days and 1-6 wk, and age-matched sham-operated rats served as controls. In a separate group of rats, an IkappaB-alpha dominant negative mutant (IkappaB-alphaM), a superrepressor of NF-kappaB activation, or pyrrolidinedithiocarbamate (PDTC), an antioxidant that can inhibit NF-kappaB activation, was administered to aortic-banded rats for 3 wk. The heart weight-to-body weight ratio was significantly increased at 5 days after aortic banding, peaked at 4 wk, and remained elevated at 6 wk compared with age-matched sham controls. Atrial natriuretic peptide and brain natriuretic peptide mRNA expressions were significantly increased after 1 wk of aortic banding, reached a maximum between 2 and 3 wk, and remained increased at 6 wk compared with age-matched sham controls. NF-kappaB activity was significantly increased at 1 day, reached a peak at 3 wk, and remained elevated at 6 wk, and IKK-beta activity was significantly increased at 1 day, peaked at 5 days, and then decreased but remained elevated at 6 wk after aortic banding compared with age-matched sham controls. Inhibiting NF-kappaB activation in vivo by cardiac transfection of IkappaB-alphaM or by PDTC treatment significantly attenuated the development of cardiac hypertrophy in vivo with a concomitant decrease in NF-kappaB activity. Our results suggest that NF-kappaB activation is required for the development of cardiac hypertrophy in vivo and that NF-kappaB could be an important target for inhibiting the development of cardiac hypertrophy in vivo.
Li
Yuehua
Y
Dept. of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Campus Box 70575, Johnson City, TN 37614-0575, USA. Li@mail.etsu.edu
Ha
Tuanzhu
T
Gao
Xiang
X
Kelley
Jim
J
Williams
David L
DL
Browder
I William
IW
Kao
Race L
RL
Li
Chuanfu
C
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000235:genetics; D008026:Ligation; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013859:Thiocarbamates / Q000494:pharmacology; D014162:Transfection
D000975:Antioxidants; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D013859:Thiocarbamates; D020097:Natriuretic Peptide, Brain; C066229:prolinedithiocarbamate; D000072000:NF-KappaB Inhibitor alpha; D009320:Atrial Natriuretic Factor; D011392:Proline; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase