AJP - Heart AJP: Lung Cellular and Molecular Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (April 15, 2004). doi:10.1152/ajpheart.01177.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/3/H1013    most recent
01177.2003v1
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 Davani, E. Y.
Right arrow Articles by Walley, K. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davani, E. Y.
Right arrow Articles by Walley, K. R.
Submitted on December 16, 2003
Accepted on April 8, 2004

NOVEL REGULATORY MECHANISM OF CARDIOMYOCYTE CONTRACTILITY INVOLVING ICAM-1 AND THE CYTOSKELETON

Ehsan Y. Davani1, Delbert R. Dorscheid1, Cheng-Han Lee1, Cornelis van Breemen1, and Keith R. Walley1*

1 University of British, Critical Care Research Laboratories, St. Paul's Hospital, Vancouver, British Columbia, Canada

* To whom correspondence should be addressed. E-mail: kwalley{at}mrl.ubc.ca.

ICAM-1 mediates interaction of cardiomyocytes with the extracellular matrix and leukocytes, and may play a role in altering contractility. To investigate this possibility rat ventricular cardiomyocytes were activated using TNF{alpha}, IL-1{beta} or LPS, washed, co-cultured with quiescent rat polymorphonuclear leukocytes (PMN) for 4 hours, and electrically stimulated to determine fractional shortening. PMN co-cultured with activated cardiomyocytes reduced control fractional shortening of 20.5±0.7% by -2.8±0.3% per adherent PMN (p<0.001). Fixing PMN with paraformaldehyde or gluteraldehyde did not prevent PMN-mediated decreases in cardiomyocyte fractional shortening. However, PMN adherence and decreased fractional shortening were prevented by anti-ICAM-1 and anti- CD18 antibodies. Reduced fractional shortening was reproduced in the absence of PMN by ICAM-1 binding using cross-linking antibodies (reduced by 36±3% from control, p<0.01). Immunofluorescent staining demonstrated increased cortical cytoskeleton-associated FAK expression following ICAM-1 cross-linking, suggesting involvement of the actin cytoskeleton. Indeed, disruption of F-actin filament assembly using cytochalasin D or latrunculin A did not prevent PMN adherence but prevented decreased fractional shortening. Inhibiting the cytoskeleton-associated Rho kinase pathway using HA-1077 prevented ICAM-1 mediated decreases in cardiomyocyte contractility, further suggesting a central role of the actin cytoskeleton. Importantly, ICAM-1 cross-linking did not alter the total intracellular Ca2+ transient during cardiomyocyte contraction but greatly increased heterogeneity of intracellular Ca2+ release. Thus, we have identified a novel regulatory mechanism of cardiomyocyte contractility involving the actin cytoskeleton as a central regulator of the normally highly coordinated pattern of sarcoplamic Ca2+ release. Cardiomyocyte ICAM-1 binding, by PMN or other ligands, induces decreased cardiomyocyte contractilty via this pathway.




This article has been cited by other articles:


Home page
 Circ. Res.Home page
J. H. Boyd, B. Kan, H. Roberts, Y. Wang, and K. R. Walley
S100A8 and S100A9 Mediate Endotoxin-Induced Cardiomyocyte Dysfunction via the Receptor for Advanced Glycation End Products
Circ. Res., May 23, 2008; 102(10): 1239 - 1246.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
R. M. Bateman, C. Tokunaga, T. Kareco, D. R. Dorscheid, and K. R. Walley
Myocardial hypoxia-inducible HIF-1{alpha}, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H448 - H456.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
G. Lin, G. P. Craig, L. Zhang, V. G. Yuen, M. Allard, J. H. McNeill, and K. M. MacLeod
Acute inhibition of Rho-kinase improves cardiac contractile function in streptozotocin-diabetic rats
Cardiovasc Res, July 1, 2007; 75(1): 51 - 58.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
J. H. Boyd, S. Mathur, Y. Wang, R. M. Bateman, and K. R. Walley
Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-{kappa}B dependent inflammatory response
Cardiovasc Res, December 1, 2006; 72(3): 384 - 393.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
Y. Wu, J. E. Ip, J. Huang, L. Zhang, K. Matsushita, C.-C. Liew, R. E. Pratt, and V. J. Dzau
Essential Role of ICAM-1/CD18 in Mediating EPC Recruitment, Angiogenesis, and Repair to the Infarcted Myocardium
Circ. Res., August 4, 2006; 99(3): 315 - 322.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. Pulinilkunnil, D. An, S. Ghosh, D. Qi, G. Kewalramani, G. Yuen, N. Virk, A. Abrahani, and B. Rodrigues
Lysophosphatidic acid-mediated augmentation of cardiomyocyte lipoprotein lipase involves actin cytoskeleton reorganization
Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2802 - H2810.
[Abstract] [Full Text] [PDF]


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