+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart



Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart



Journal of the American College of Cardiology 58(9): 977-986



The purpose of this study was to test the ability of insulin-like growth factor (IGF)-1/hepatocyte growth factor (HGF) to activate resident endogenous porcine cardiac stem/progenitor cells (epCSCs) and to promote myocardial repair through a clinically applicable intracoronary injection protocol in a pig model of myocardial infarction (MI) relevant to human disease. In rodents, cardiac stem/progenitor cell (CSC) transplantation as well as in situ activation through intramyocardial injection of specific growth factors has been shown to result in myocardial regeneration after acute myocardial infarction (AMI). Acute MI was induced in pigs by a 60-min percutaneous transluminal coronary angiography left anterior descending artery occlusion. The IGF-1 and HGF were co-administered through the infarct-related artery in a single dose (ranging from 0.5 to 2 μg HGF and 2 to 8 μg IGF-1) 30 min after coronary reperfusion. Pigs were sacrificed 21 days later for dose-response relationship evaluation by immunohistopathology or 2 months later for cardiac function evaluation by cardiac magnetic resonance imaging. The IGF-1/HGF activated c-kit positive-CD45 negative epCSCs and increased their myogenic differentiation in vitro. The IGF-1/HGF, in a dose-dependent manner, improved cardiomyocyte survival, and reduced fibrosis and cardiomyocyte reactive hypertrophy. It significantly increased c-kit positive-CD45 negative epCSC number and fostered the generation of new myocardium (myocytes and microvasculature) in infarcted and peri-infarct/border regions at 21 and 60 days after AMI. The IGF-1/HGF reduced infarct size and improved left ventricular function at 2 months after AMI. In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 052961217

Download citation: RISBibTeXText

PMID: 21723061

DOI: 10.1016/j.jacc.2011.05.013


Related references

Sustained delivery of insulin-like growth factor-1/hepatocyte growth factor stimulates endogenous cardiac repair in the chronic infarcted pig heart. Journal of Cardiovascular Translational Research 7(2): 232-241, 2014

Sustained delivery of insulin-like growth factor-1/hepatocyte growth factor promotes endogenous cardiac repair and regeneration in the chronic ischemic heart. European Heart Journal 34(Suppl 1): P1450-P1450, 2013

A collagen cardiac patch incorporating alginate microparticles permits the controlled release of hepatocyte growth factor and insulin-like growth factor-1 to enhance cardiac stem cell migration and proliferation. Journal of Tissue Engineering and Regenerative Medicine 12(1): E384-E394, 2018

MSCs transfected with hepatocyte growth factor or vascular endothelial growth factor improve cardiac function in the infarcted porcine heart by increasing angiogenesis and reducing fibrosis. International Journal of Cardiology 167(6): 2524-2532, 2013

Activation of hepatic stem cell compartment in the rat: role of transforming growth factor alpha, hepatocyte growth factor, and acidic fibroblast growth factor in early proliferation. Cell Growth & Differentiation 4(7): 555-561, 1993

Rapid induction of mRNAs for liver regeneration factor and insulin-like growth factor binding protein-1 in primary cultures of rat hepatocytes by hepatocyte growth factor and epidermal growth factor. Hepatology 20(4 Part 1): 955-960, 1994

Improved function and myocardial repair of infarcted heart by intracoronary injection of mesenchymal stem cell-derived growth factors. Journal of Cardiovascular Translational Research 3(5): 547-558, 2010

Mesenchymal stem cells modified with stromal cell-derived factor 1 alpha improve cardiac remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Molecules and Cells 29(1): 9, 2010

Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circulation Research 97(7): 663-673, 2005

Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival (vol 97, pg 663, 2005). Circulation Research 98(3): E27, 2006

Effect of transforming growth factor-beta1, insulin-like growth factor-I, and hepatocyte growth factor on proteoglycan production and regulation in canine melanoma cell lines. American Journal of Veterinary Research 63(8): 1151-1158, 2002

Effect of transforming growth factor-b1, insulin-like growth factor-I, and hepatocyte growth factor on proteoglycan production and regulation in canine melanoma cell lines. American Journal of Veterinary Research 63(8): 51-8, 2002

Effect of transforming growth factor-1, insulin-like growth factor-I, and hepatocyte growth factor on proteoglycan production and regulation in canine melanoma cell lines. American Journal of Veterinary Research 63(8): 1151-1158, 2002

The in vivo effect of hepatotrophic factors augmenter of liver regeneration, hepatocyte growth factor, and insulin-like growth factor-II on liver natural killer cell functions. Hepatology 25(2): 411-415, 1997

Hepatocyte growth factor-induced mesenchymal-epithelial transition factor activation leads to insulin-like growth factor 1 receptor inhibitor unresponsiveness in gastric cancer cells. Oncology Letters 16(5): 5983-5991, 2018