AJP - Heart Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (December 27, 2002). doi:10.1152/ajpheart.00885.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/4/H1429    most recent
00885.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
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 Google Scholar
Google Scholar
Right arrow Articles by Su, E. J.
Right arrow Articles by Liau, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Su, E. J.
Right arrow Articles by Liau, G.
Submitted on October 8, 2002
Accepted on December 17, 2002

Gene therapy vector-mediated expression of insulin-like growth factors protects cardiomyocytes from apoptosis and enhances neovascularization

Enming J. Su1, Cathy L. Cioffi2, Steingrimur Stefansson1, Nanette Mittereder1, Michelle Garay2, D Hreniuk2, and Gene Liau1*

1 Genetic Therapy Inc., Novartis, Gaithersburg, MD, USA
2 Metabolic and Cardiovascular diseases, Novartis, Summit, NJ, USA

* To whom correspondence should be addressed. E-mail: gene.liau{at}pharma.novartis.com.

Insulin-like growth factor I (IGFI) and II (IGFII) are single-chain polypeptide growth factors that regulate pleiotropic cellular responses. We have characterized the effect of recombinant IGF proteins as well as third-generation adenoviral vectors encoding either IGF-I or IGF-II genes, on cardiomyocyte apoptosis and on angiogenesis. We found that endothelial cells cultured in the presence of the extracellular protein, laminin exhibit a robust respond to IGF-I and II proteins via enhanced cell migration and angiogenic outgrowth. Furthermore, IGF vectors greatly enhanced neovascularization in an in vivo matrigel model. Transduction of cardiomyocytes with the IGF adenoviral vectors resulted in a dose- and time-dependent increase in the expression of IGF-I or IGF-II protein. This correlated with abrogation of apoptosis induced by ischemia/reoxygenation, ceramide or heat shock with optimal inhibition of around 80%. We conclude that gene transfer of IGF-I and IGF-II is a plausible strategy for the local delivery of IGFs to treat ischemic heart disease and heart failure by stimulating angiogenesis and protecting cardiomyocytes from cell death.




This article has been cited by other articles:


Home page
 Stem CellsHome page
C. Gandia, A. Arminan, J. M. Garcia-Verdugo, E. Lledo, A. Ruiz, M D. Minana, J. Sanchez-Torrijos, R. Paya, V. Mirabet, F. Carbonell-Uberos, et al.
Human Dental Pulp Stem Cells Improve Left Ventricular Function, Induce Angiogenesis, and Reduce Infarct Size in Rats with Acute Myocardial Infarction
Stem Cells, March 1, 2008; 26(3): 638 - 645.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Schonherr, C. Sunderkotter, R. V. Iozzo, and L. Schaefer
Decorin, a Novel Player in the Insulin-like Growth Factor System
J. Biol. Chem., April 22, 2005; 280(16): 15767 - 15772.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
Y. Cao, A. Hong, H. Schulten, and M. J. Post
Update on therapeutic neovascularization
Cardiovasc Res, February 15, 2005; 65(3): 639 - 648.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
P. Delafontaine, Y.-H. Song, and Y. Li
Expression, Regulation, and Function of IGF-1, IGF-1R, and IGF-1 Binding Proteins in Blood Vessels
Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 435 - 444.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.