| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
is toxic via receptor 1 and protective via receptor 2 in a murine model of myocardial infarction
1 Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka-shi, Fukuoka-ken, Japan
2 Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo-shi, Hokkaido, Japan
* To whom correspondence should be addressed. E-mail: kubotat{at}cardiol.med.kyushu-u.ac.jp.
Tumor necrosis factor (TNF)-
induced in damaged myocardium has been considered to be cardiotoxic. TNF- initiates its biological effects by binding two distinct receptors; R1 (p55) and R2 (p75). Although TNF- has been shown to be cardiotoxic via R1-mediated pathways, little is known about the roles of R2-mediated pathways in myocardial infarction (MI). We created MI in R1-knockout (KO), R2KO, and wild type (WT) mice by ligating the left coronary artery. Functional, histological, and biochemical analyses were performed 4 weeks after ligation. Although infarct size was not different among WT, R1KO, and R2KO mice, post-MI survival was significantly improved in R1KO but not R2KO mice. R1KO significantly ameliorated contractile dysfunction after MI, while R2KO significantly exaggerated ventricular dilatation and dysfunction. Myocyte hypertrophy and interstitial fibrosis in non-infarct myocardium was exacerbated in R2KO but not in R1KO mice. Expression of R1, which was not affected by MI and was nullified in R1KO mice, was significantly up-regulated in R2KO mice. In contrast, expression of R2, which was significantly up-regulated by MI and was nullified in R2KO mice, was unaffected in R1KO mice. Meanwhile, TNF- expression, which was significantly up-regulated in non-infarct myocardium after MI, was not affected by R1KO or R2KO. However, transcript levels of IL-6, IL-1
, TGF-, and MCP-1, which were significantly up-regulated after MI, were significantly down-regulated in R1KO mice. In contrast, transcript levels of IL-6 and IL-1 were significantly further up-regulated in R2KO mice. TNF- is toxic via R1 and protective via R2 in a murine model of MI. Selective blockade of R1 may be a candidate therapeutic intervention for cardiovascular diseases.
This article has been cited by other articles:
|
|
 |
|
  K. Hoetzenecker, C. Adlbrecht, M. Lichtenauer, S. Hacker, W. Hoetzenecker, A. Mangold, S. Nickl, A. Mitterbauer, M. Zimmermann, I. M. Lang, et al. Levels of sCD40, sCD40L, TNF{alpha}, and TNF-RI in the Culprit Coronary Artery During Myocardial Infarction Lab Med, November 1, 2009; 40(11): 660 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lacerda, S. Somers, L. H. Opie, and S. Lecour Ischaemic postconditioning protects against reperfusion injury via the SAFE pathway Cardiovasc Res, November 1, 2009; 84(2): 201 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Fildes, S. M. Shaw, N. Yonan, and S. G. Williams The Immune System and Chronic Heart Failure: Is the Heart in Control? J. Am. Coll. Cardiol., March 24, 2009; 53(12): 1013 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schulz and G. Heusch Tumor Necrosis Factor-{alpha} and Its Receptors 1 and 2: Yin and Yang in Myocardial Infarction? Circulation, March 17, 2009; 119(10): 1355 - 1357. [Full Text] [PDF]
|
|
|
|
|
|
M. Wang, P. R. Crisostomo, T. A. Markel, Y. Wang, and D. R. Meldrum Mechanisms of Sex Differences in TNFR2-Mediated Cardioprotection Circulation, September 30, 2008; 118(14_suppl_1): S38 - S45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Plaisance, C. Morandi, C. Murigande, and M. Brink TNF-{alpha} increases protein content in C2C12 and primary myotubes by enhancing protein translation via the TNF-R1, PI3K, and MEK Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E241 - E250. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
