AJP - Heart Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (June 2, 2006). doi:10.1152/ajpheart.00043.2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/4/H1972    most recent
00043.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, Z.
Right arrow Articles by Protter, A. A
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, Z.
Right arrow Articles by Protter, A. A
Submitted on January 9, 2006
Accepted on May 26, 2006

Selective Inhibition of p38{alpha} MAPK Improves Cardiac Function and Reduces Myocardial Apoptosis in Rat Model of Myocardial Injury

Zhihe Li1*, Jing Ying Ma1, Irene Kerr1, Sarvajit Chakravarty1, Sundeep Dugar1, George Schreiner1, and Andrew A Protter1

1 Pharmacology, Scios Inc., Fremont, California, United States

* To whom correspondence should be addressed. E-mail: zli9{at}scius.jnj.com.

p38 mitogen-activated protein kinase (MAPK) is activated during heart diseases which might associate with myocardial damage and deterioration of cardiac function. In a rat model of myocardial injury, we have investigated cardioprotective effects of the inhibition of p38 MAPK using a novel, oral available p38{alpha} MAPK inhibitor. Rats were treated with Nw-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg/day) in drinking water plus 1% salt for 14 days and angiotensin II (AngII, 0.5 mg/kg/day) for 3 days. A selective p38{alpha} MAPK inhibitor, SD-282 (60 mg/kg) was administrated orally, twice a day for 4 days, starting a day prior to AngII administration. The cardioprotective effects of p38{alpha} MAPK inhibition were evaluated by improvement of cardiac function, reduction of inflammatory cell infiltration and cardiomyocyte apoptosis. SD-282 significantly improved cardiac function indicated by increasing stroke volume (SV), cardiac output (CO), ejection fraction (EF), stroke work (SW) and significantly decreasing arterial elastance (Ea). SD-282 also significantly reduced macrophage infiltration as judged by reduction of a specific marker, ED-1 positive staining cells (p<0.05) in the myocardium. Furthermore, cardiomyocyte apoptosis as indicated by caspase-3 immunohistochemical staining was abolished by SD-282 and this effect may contribute to the reduction of myocardial damage evaluated by imaging analysis (p<0.05 in both cases). Data suggest that p38{alpha} MAPK may play a critical role in the pathogenesis of cardiac dysfunction. Inhibition of p38{alpha} MAPK may be used as a novel cardioprotective strategy in attenuation of inflammatory response and deterioration of cardiac function that occurs in acute cardiovascular disease such as myocardial infarction.




This article has been cited by other articles:


Home page
 Circ. Res.Home page
P. Krishnamurthy, J. Rajasingh, E. Lambers, G. Qin, D. W. Losordo, and R. Kishore
IL-10 Inhibits Inflammation and Attenuates Left Ventricular Remodeling After Myocardial Infarction via Activation of STAT3 and Suppression of HuR
Circ. Res., January 30, 2009; 104(2): e9 - e18.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. Shinmura, K. Tamaki, and R. Bolli
Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1
Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2348 - H2355.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
L. Gu, V. Pandey, D. L. Geenen, S. A.K. Chowdhury, and M. R. Piano
Cigarette smoke-induced left ventricular remodelling is associated with activation of mitogen-activated protein kinases
Eur J Heart Fail, November 1, 2008; 10(11): 1057 - 1064.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
S. W. Rabkin and M. Y. C. Tsang
The action of nitric oxide to enhance cell survival in chick cardiomyocytes is mediated through a cGMP and ERK1/2 pathway while p38 mitogen-activated protein kinase-dependent pathways do not alter cell death
Exp Physiol, July 1, 2008; 93(7): 834 - 842.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
W. Chai, Y. Wu, G. Li, W. Cao, Z. Yang, and Z. Liu
Activation of p38 mitogen-activated protein kinase abolishes insulin-mediated myocardial protection against ischemia-reperfusion injury
Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E183 - E189.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
W. Mao, S. Fukuoka, C. Iwai, J. Liu, V. K. Sharma, S.-S. Sheu, M. Fu, and C.-s. Liang
Cardiomyocyte apoptosis in autoimmune cardiomyopathy: mediated via endoplasmic reticulum stress and exaggerated by norepinephrine
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1636 - H1645.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
Y. Asaumi, Y. Kagaya, M. Takeda, N. Yamaguchi, H. Tada, K. Ito, J. Ohta, T. Shiroto, K. Shirato, N. Minegishi, et al.
Protective Role of Endogenous Erythropoietin System in Nonhematopoietic Cells Against Pressure Overload-Induced Left Ventricular Dysfunction in Mice
Circulation, April 17, 2007; 115(15): 2022 - 2032.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.