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PMID: 20536456 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Thymosin beta4: a key factor for protective effects of eEPCs in acute and chronic ischemia.

Annals of the New York Academy of Sciences ·Vol. 1194 ·2010-04-00 ·Pages 105-11

Hinkel R, Bock-Marquette I, Hatzopoulos AK, Hazopoulos AK, Kupatt C

Abstract

Acute myocardial infarction is still one of the leading causes of death in the industrial nations. Even after successful revascularization, myocardial ischemia results in a loss of cardiomyocytes and scar formation. Embryonic EPCs (eEPCs), retroinfused into the ischemic region of the pig heart, provided rapid paracrine benefit to acute and chronic ischemia in a PI-3K/Akt-dependent manner. In a model of acute myocardial ischemia, infarct size and loss of regional myocardial function decreased after eEPC application, unless cell pre-treatment with thymosin beta4 shRNA was performed. Thymosin beta4 peptide retroinfusion mimicked the eEPC-derived improvement of infarct size and myocardial function. In chronic ischemia (rabbit model), eEPCs retroinfused into the ischemic hindlimb enhanced capillary density, collateral growth, and perfusion. Therapeutic neovascularization was absent when thymosin beta4 shRNA was introduced into eEPCs before application. In conclusion, eEPCs are capable of acute and chronic ischemia protection in a thymosin beta4 dependent manner.

MeSH Terms
Animals Capillaries/physiopathology Embryonic Stem Cells/metabolism Heart/physiopathology Hindlimb/blood supply,physiopathology Ischemia Myocardial Ischemia/physiopathology,therapy Myocardium/metabolism Myocytes, Cardiac/metabolism Phosphatidylinositol 3-Kinases/pharmacology Proto-Oncogene Proteins c-akt/metabolism Rabbits Swine Thymosin/metabolism
Chemicals
thymosin beta(4) Thymosin Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins c-akt
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hinkel Rabea
Internal Medicine I, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.
Bock-Marquette Ildiko
Hatzopoulos Antonis K
Hazopoulos Antonis K
Kupatt Christian
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Article Info
Journal
Annals of the New York Academy of Sciences
Abbr.
Ann N Y Acad Sci
ISSN
1749-6632
DOI
10.1111/j.1749-6632.2010.05489.x
Published
2010-04-00
Pages
105-11
Language
English
Region
United States
NLM ID
7506858
PMCID
PMC3601487
Subset
IM
Grants
NHLBI NIH HHS · R01 HL083958-03 · United States
NHLBI NIH HHS · R01 HL083958-04 · United States
NHLBI NIH HHS · R01 HL083958-05 · United States
NHLBI NIH HHS · HL083958 · United States
NHLBI NIH HHS · U01 HL100398-02 · United States
NHLBI NIH HHS · R01 HL083958-02 · United States
NHLBI NIH HHS · U01 HL100398 · United States
NHLBI NIH HHS · U01 HL100398-03 · United States
NHLBI NIH HHS · U01 HL100398-01 · United States
NHLBI NIH HHS · R01 HL083958 · United States
NHLBI NIH HHS · R01 HL083958-01 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1111/j.1749-6632.2010.05489.x PMC Full Text View journal details
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