| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
B improves left ventricular remodeling and cardiac dysfunction after myocardial infarction
1 Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
2 Medical Molecular Design, Inc., Tokyo, Japan
* To whom correspondence should be addressed. E-mail: isobemi.cvm{at}tmd.ac.jp.
Background -Several studies have demonstrated that NF-
B is substantially involved in the progression of cardiac remodeling; however, it remains uncertain whether the continuous inhibition of NF-B is effective for the prevention of myocardial remodeling.
Methods -Myocardial infarction (MI) was produced by ligation of the left anterior coronary artery of rats. IMD-0354 (10 mg/kg/day), a novel phosphorylation inhibitor of IB that acts via inhibition of IKK
, was injected intraperitoneally starting 24 hours after induction of MI for 28 days.
Results - After 28 days, IMD-0354-treated group showed significantly improved survival rate compared to that of vehicle-treated group (p < 0.05). Although infarct size was similar in both groups, improved left ventricular (LV) remodeling and diastolic dysfunction, as indicated by smaller LV cavity (LV end-diastolic area: vehicle, 74.13 ± 3.57 mm2; IMD-0354, 55.00 ± 3.73 mm2; p < 0.05), smaller E/A ratio (vehicle, 3.87 ± 0.26; IMD-0354, 2.61 ± 0.24; p < 0.05), and lower plasma brain natriuretic peptide level (vehicle, 167.63 ± 14.87 pg/ml; IMD-0354, 110.75 ± 6.41 pg/ml; p < 0.05), were observed in the IMD-0354-treated group. Moreover, fibrosis, accumulation of macrophages and expression of several factors (TGF-1, MCP-1, MMP-9 and MMP-2) in the noninfarcted myocardium was remarkably inhibited by IMD-0354.
Conclusions - Inhibition of NF-B activation may reduce the proinflammatory reactions and modulate the extracellular matrix and provide an effective approach to prevent adverse cardiac remodeling after MI.
This article has been cited by other articles:
|
|
 |
|
  Y. Maekawa, N. Mizue, A. Chan, Y. Shi, Y. Liu, S. Dawood, M. Chen, F. Dawood, G. de Couto, G. H. Li, et al. Survival and Cardiac Remodeling After Myocardial Infarction Are Critically Dependent on the Host Innate Immune Interleukin-1 Receptor-Associated Kinase-4 Signaling: A Regulator of Bone Marrow-Derived Dendritic Cells Circulation, October 6, 2009; 120(14): 1401 - 1414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mahmoodzadeh, S. Fritschka, E. Dworatzek, T. H. Pham, E. Becher, A. Kuehne, M. M. Davidson, and V. Regitz-Zagrosek Nuclear Factor-{kappa}B Regulates Estrogen Receptor-{alpha} Transcription in the Human Heart J. Biol. Chem., September 11, 2009; 284(37): 24705 - 24714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Timmers and D. P.V. de Kleijn Response to the Letter by Frantz and Bauersachs Circ. Res., June 5, 2009; 104(11): e61 - e61. [Full Text] [PDF]
|
|
|
|
|
|
L. Timmers, J. K. van Keulen, I. E. Hoefer, M. F.L. Meijs, B. van Middelaar, K. den Ouden, C. J.A. van Echteld, G. Pasterkamp, and D. P.V. de Kleijn Targeted Deletion of Nuclear Factor {kappa}B p50 Enhances Cardiac Remodeling and Dysfunction Following Myocardial Infarction Circ. Res., March 13, 2009; 104(5): 699 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Moss, W. E. Stansfield, M. S. Willis, R.-H. Tang, and C. H. Selzman IKKbeta inhibition attenuates myocardial injury and dysfunction following acute ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2248 - H2253. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
