Thymosin beta4: a key factor for protective effects of eEPCs in acute and chronic ischemia.
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.
Hinkel
Rabea
R
Internal Medicine I, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.
Bock-Marquette
Ildiko
I
Hatzopoulos
Antonis K
AK
Hazopoulos
Antonis K
AK
Kupatt
Christian
C
D000818:Animals; D002196:Capillaries / Q000503:physiopathology; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D006614:Hindlimb / Q000098:blood supply / Q000503:physiopathology; D007511:Ischemia; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011817:Rabbits; D013552:Swine; D013947:Thymosin / Q000378:metabolism*; D000099201:Thymosin beta(4)
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013947:Thymosin; D000099201:Thymosin beta(4)