Ischemia-reperfusion injury and pregnancy initiate time-dependent and robust signs of up-regulation of cardiac progenitor cells

To explore how cardiac regeneration and cell turnover adapts to disease, different forms of stress were studied for their effects on the cardiac progenitor cell markers c-Kit and Isl1, the early cardiomyocyte marker Nkx2.5, and mast cells. Adult female rats were examined during pregnancy, after myoc...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2012-05, Vol.7 (5), p.e36804-e36804
Main Authors: Genead, Rami, Fischer, Helene, Hussain, Alamdar, Jaksch, Marie, Andersson, Agneta B, Ljung, Karin, Bulatovic, Ivana, Franco-Cereceda, Anders, Elsheikh, Elzafir, Corbascio, Matthias, Smith, C I Edvard, Sylvén, Christer, Grinnemo, Karl-Henrik
Format: Article
Language:English
Subjects:
Anesthesiology
Angiogenesis
Animals
Antigens, Differentiation - biosynthesis
Apoptosis
Biology
c-Kit protein
Cardiology
Cardiomyocytes
Cell activation
Cells (biology)
Coronary artery disease
Correlation
Female
Growth factors
Heart
Heart attack
Heart attacks
Heart diseases
Heart surgery
Hepatocyte growth factor
Hepatocyte Growth Factor - biosynthesis
Homeobox Protein Nkx-2.5
Homeodomain Proteins - biosynthesis
Injuries
Insulin
Insulin-like growth factor I
Insulin-Like Growth Factor I - biosynthesis
Insulin-like growth factors
Ischemia
Islet-1 protein
Laboratory animals
Mast cells
Mechanical properties
Medical treatment
Medicin och hälsovetenskap
Medicine
mRNA
Myocardial infarction
Myocardial Infarction - metabolism
Myocardial Infarction - pathology
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - pathology
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Nkx2.5 protein
Physiology
Pregnancy
Pregnancy Complications, Cardiovascular - metabolism
Pregnancy Complications, Cardiovascular - pathology
Pregnant women
Progenitor cells
Proto-Oncogene Proteins c-kit - biosynthesis
Rats
Rats, Sprague-Dawley
Regeneration
Reperfusion
Reperfusion injury
RNA
Rodents
Smooth muscle
Stem cells
Stem Cells - metabolism
Stem Cells - pathology
Transcription factors
Transcription Factors - biosynthesis
Up-Regulation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:To explore how cardiac regeneration and cell turnover adapts to disease, different forms of stress were studied for their effects on the cardiac progenitor cell markers c-Kit and Isl1, the early cardiomyocyte marker Nkx2.5, and mast cells. Adult female rats were examined during pregnancy, after myocardial infarction and ischemia-reperfusion injury with/out insulin like growth factor-1(IGF-1) and hepatocyte growth factor (HGF). Different cardiac sub-domains were analyzed at one and two weeks post-intervention, both at the mRNA and protein levels. While pregnancy and myocardial infarction up-regulated Nkx2.5 and c-Kit (adjusted for mast cell activation), ischemia-reperfusion injury induced the strongest up-regulation which occurred globally throughout the entire heart and not just around the site of injury. This response seems to be partly mediated by increased endogenous production of IGF-1 and HGF. Contrary to c-Kit, Isl1 was not up-regulated by pregnancy or myocardial infarction while ischemia-reperfusion injury induced not a global but a focal up-regulation in the outflow tract and also in the peri-ischemic region, correlating with the up-regulation of endogenous IGF-1. The addition of IGF-1 and HGF did boost the endogenous expression of IGF and HGF correlating to focal up-regulation of Isl1. c-Kit expression was not further influenced by the exogenous growth factors. This indicates that there is a spatial mismatch between on one hand c-Kit and Nkx2.5 expression and on the other hand Isl1 expression. In conclusion, ischemia-reperfusion injury was the strongest stimulus with both global and focal cardiomyocyte progenitor cell marker up-regulations, correlating to the endogenous up-regulation of the growth factors IGF-1 and HGF. Also pregnancy induced a general up-regulation of c-Kit and early Nkx2.5+ cardiomyocytes throughout the heart. Utilization of these pathways could provide new strategies for the treatment of cardiac disease.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0036804