Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation

Elena Dolmatova, Gaelle Spagnol, Daniela Boassa, Jennifer R. Baum, Kimberly Keith, Cinzia Ambrosi, Maria I. Kontaridis, Paul L Sorgen, Gina E. Sosinsky, Heather S. Duffy

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Fibrosis following myocardial infarction is associated with increases in arrhythmias and sudden cardiac death. Initial steps in the development of fibrosis are not clear; however, it is likely that cardiac fibroblasts play an important role. In immune cells, ATP release from pannexin 1 (Panx1) channels acts as a paracrine signal initiating activation of innate immunity. ATP has been shown in noncardiac systems to initiate fibroblast activation. Therefore, we propose that ATP release through Panx1 channels and subsequent fibroblast activation in the heart drives the development of fibrosis in the heart following myocardial infarction. We identified for the first time that Panx1 is localized within sarcolemmal membranes of canine cardiac myocytes where it directly interacts with the postsynaptic density 95/Drosophila disk large/zonula occludens-1-containing scaffolding protein synapseassociated protein 97 via its carboxyl terminal domain (amino acids 300-357). Induced ischemia rapidly increased glycosylation of Panx1, resulting in increased trafficking to the plasma membrane as well as increased interaction with synapse-associated protein 97. Cellular stress enhanced ATP release from myocyte Panx1 channels, which, in turn, causes fibroblast transformation to the activated myofibroblast phenotype via activation of the MAPK and p53 pathways, both of which are involved in the development of cardiac fibrosis. ATP release through Panx1 channels in cardiac myocytes during ischemia may be an early paracrine event leading to profibrotic responses to ischemic cardiac injury.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume303
Issue number10
DOIs
StatePublished - Nov 15 2012

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Cardiac Myocytes
Fibroblasts
Adenosine Triphosphate
Fibrosis
Ischemia
Myocardial Infarction
Post-Synaptic Density
Myofibroblasts
Tight Junctions
Sudden Cardiac Death
Glycosylation
Innate Immunity
Muscle Cells
Drosophila
Canidae
Cardiac Arrhythmias
Proteins
Cell Membrane
Phenotype
Amino Acids

Keywords

  • Fibrosis
  • Ischemia
  • Paracrine signal
  • Sudden cardiac death

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation. / Dolmatova, Elena; Spagnol, Gaelle; Boassa, Daniela; Baum, Jennifer R.; Keith, Kimberly; Ambrosi, Cinzia; Kontaridis, Maria I.; Sorgen, Paul L; Sosinsky, Gina E.; Duffy, Heather S.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 303, No. 10, 15.11.2012.

Research output: Contribution to journalArticle

Dolmatova, E, Spagnol, G, Boassa, D, Baum, JR, Keith, K, Ambrosi, C, Kontaridis, MI, Sorgen, PL, Sosinsky, GE & Duffy, HS 2012, 'Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation', American Journal of Physiology - Heart and Circulatory Physiology, vol. 303, no. 10. https://doi.org/10.1152/ajpheart.00251.2012
Dolmatova, Elena ; Spagnol, Gaelle ; Boassa, Daniela ; Baum, Jennifer R. ; Keith, Kimberly ; Ambrosi, Cinzia ; Kontaridis, Maria I. ; Sorgen, Paul L ; Sosinsky, Gina E. ; Duffy, Heather S. / Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation. In: American Journal of Physiology - Heart and Circulatory Physiology. 2012 ; Vol. 303, No. 10.
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