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Antiarrhythmic effect of growth factor-supplemented cardiac progenitor cells in chronic infarcted heart
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 310:H1622-H1648
- Publication Year :
- 2016
- Publisher :
- American Physiological Society, 2016.
-
Abstract
- c-Kitpos cardiac progenitor cells (CPCs) represent a successful approach in healing the infarcted heart and rescuing its mechanical function, but electrophysiological consequences are uncertain. CPC mobilization promoted by hepatocyte growth factor (HGF) and IGF-1 improved electrogenesis in myocardial infarction (MI). We hypothesized that locally delivered CPCs supplemented with HGF + IGF-1 (GFs) can concur in ameliorating electrical stability of the regenerated heart. Adult male Wistar rats (139 rats) with 4-wk-old MI or sham conditions were randomized to receive intramyocardial injection of GFs, CPCs, CPCs + GFs, or vehicle (V). Enhanced green fluorescent protein-tagged CPCs were used for cell tracking. Vulnerability to stress-induced arrhythmia was assessed by telemetry-ECG. Basic cardiac electrophysiological properties were examined by epicardial multiple-lead recording. Hemodynamic function was measured invasively. Hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. Compared with V and at variance with individual CPCs, CPCs + GFs approximately halved arrhythmias in all animals, restoring cardiac anisotropy toward sham values. GFs alone reduced arrhythmias by less than CPCs + GFs, prolonging ventricular refractoriness without affecting conduction velocity. Concomitantly, CPCs + GFs reactivated the expression levels of Connexin-43 and Connexin-40 as well as channel proteins of key depolarizing and repolarizing ion currents differently than sole GFs. Mechanical function and anatomical remodeling were equally improved by all regenerative treatments, thus exhibiting a divergent behavior relative to electrical aspects. Conclusively, we provided evidence of distinctive antiarrhythmic action of locally injected GF-supplemented CPCs, likely attributable to retrieval of Connexin-43, Connexin-40, and Cav1.2 expression, favoring intercellular coupling and spread of excitation in mended heart.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Cardiac progenitors
Physiology
medicine.medical_treatment
Cardiac gap junction connexion
030204 cardiovascular system & hematology
Cardiac progenitor cell
03 medical and health sciences
0302 clinical medicine
Physiology (medical)
Internal medicine
Animals
Medicine
Myocytes, Cardiac
Myocardial infarction
Insulin-Like Growth Factor I
Rats, Wistar
Hepatocyte Growth Factor
business.industry
Stem Cells
Growth factor
Growth factors and cytokine
medicine.disease
cardiac gap junction connexin
Rats
030104 developmental biology
Connexin 43
Infarcted heart
Cardiology
Hepatocyte growth factor
Antiarrhythmic effect
Cardiology and Cardiovascular Medicine
business
Local injection
Anti-Arrhythmia Agents
Arrhythmia
medicine.drug
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 310
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....1cf6bba7299e8fb73755361c18a49216