Am J Physiol Cell Physiol Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Am J Physiol Cell Physiol 292: C1799-C1808, 2007. First published January 17, 2007; doi:10.1152/ajpcell.00166.2006
0363-6143/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/5/C1799    most recent
00166.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
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 ISI Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by LaFramboise, W. A.
Right arrow Articles by Becich, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by LaFramboise, W. A.
Right arrow Articles by Becich, M. J.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Cardiac fibroblasts influence cardiomyocyte phenotype in vitro

W. A. LaFramboise,1,2 D. Scalise,2 P. Stoodley,3 S. R. Graner,4 R. D. Guthrie,5 J. A. Magovern,2 and M. J. Becich1

1Department of Pathology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Shadyside Hospital, Pittsburgh; and Departments of 2Cardiothoracic Surgery, 3Genomic Sciences, 4Pathology, and 5Pediatrics, Drexel University School of Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania

Submitted 10 April 2006 ; accepted in final form 11 January 2007

Cardiac fibroblasts impact myocardial development and remodeling through intercellular contact with cardiomyocytes, but less is known about noncontact, profibrotic signals whereby fibroblasts alter cardiomyocyte behavior. Fibroblasts and cardiomyocytes were harvested from newborn rat ventricles and separated by serial digestion and gradient centrifugation. Cardiomyocytes were cultured in 1) standard medium, 2) standard medium diluted 1:1 with PBS, or 3) standard medium diluted 1:1 with medium conditioned ≥72 h by cardiac fibroblasts. Serum concentrations were held constant under all media conditions, and complete medium exchanges were performed daily. Cardiomyocytes began contracting within 24 h at clonal or mass densities with <5% of cells expressing vimentin. Immunocytochemical analysis revealed progressive expression of {alpha}-smooth muscle actin in cardiomyocytes after 24 h in all conditions. Only cardiomyocytes in fibroblast-conditioned medium stopped contracting by 72 h. There was a significant, sustained increase in vimentin expression specific to these cultures (means ± SD: conditioned 46.3 ± 6.0 vs. control 5.3 ± 2.9%, P < 0.00025) typically with cardiac myosin heavy chain coexpression. Proteomics assays revealed 10 cytokines (VEGF, GRO/KC, monocyte chemoattractant protein-1, leptin, macrophage inflammatory protein-1{alpha}, IL-6, IL-10, IL-12p70, IL-17, and tumor necrosis factor-{alpha}) at or below detection levels in unconditioned medium that were significantly elevated in fibroblast-conditioned medium. Latent transforming growth factor-beta and RANTES were present in unconditioned medium but rose to higher levels in conditioned medium. Only granulocyte-macrophage colony-stimulating factor was present above threshold levels in standard medium but decreased with fibroblast conditioning. These data indicated that under the influence of fibroblast-conditioned medium, cardiomyocytes exhibited marked hypertrophy, diminished contractile capacity, and phenotype plasticity distinct from the dedifferentiation program present under standard culture conditions.

proteomics; myosin heavy chain; vimentin; myofibroblast; primary culture; dedifferentiation; plasticity



Address for reprint requests and other correspondence: W. A. LaFramboise, Univ. of Pittsburgh School of Medicine, Shadyside Hospital, Dept. of Pathology, West Wing G Floor, Rm. WG21.3, 5230 Center Ave., Pittsburgh, PA 15232 (e-mail: laframboisewa{at}upmc.edu)




This article has been cited by other articles:


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
K. Shivakumar, S. J. Sollott, M. Sangeetha, S. Sapna, B. Ziman, S. Wang, and E. G. Lakatta
Paracrine effects of hypoxic fibroblast-derived factors on the MPT-ROS threshold and viability of adult rat cardiac myocytes
Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2653 - H2658.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
K. Venkatachalam, S. Mummidi, D. M. Cortez, S. D. Prabhu, A. J. Valente, and B. Chandrasekar
Resveratrol inhibits high glucose-induced PI3K/Akt/ERK-dependent interleukin-17 expression in primary mouse cardiac fibroblasts
Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2078 - H2087.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
K. B. Walsh and J. Zhang
Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C
Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1010 - H1017.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
S. Roy, S. Khanna, T. Rink, J. Radtke, W. T. Williams, S. Biswas, R. Schnitt, A. R. Strauch, and C. K. Sen
p21waf1/cip1/sdi1 as a Central Regulator of Inducible Smooth Muscle Actin Expression and Differentiation of Cardiac Fibroblasts to Myofibroblasts
Mol. Biol. Cell, December 1, 2007; 18(12): 4837 - 4846.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.