Thymosin β4 Is an Essential Paracrine Factor of Embryonic Endothelial Progenitor Cell–Mediated Cardioprotection
Rabea Hinkel,Chiraz El-Aouni,Tonia Olson,Jan Horstkotte,Stefan Mayer,Sebastian Muller,Michael Willhauck,Christine Spitzweg,Franz Josef Gildehaus,Wolfgang Münzing,Ewald Hannappel,Ildiko Bock-Marquette,J. Michael DiMaio,Antonis K. Hatzopoulos,Peter Boekstegers,Christian Kupatt +15 more
TLDR
The findings show that short-term cardioprotection derived by regional application of eEPCs can be attributed, at least in part, to Tβ4.Abstract:
Background— Prolonged myocardial ischemia results in cardiomyocyte loss despite successful revascularization. We have reported that retrograde application of embryonic endothelial progenitor cells (eEPCs) provides rapid paracrine protection against ischemia-reperfusion injury. Here, we investigated the role of thymosin β4 (Tβ4) as a mediator of eEPC-mediated cardioprotection. Methods and Results— In vitro, neonatal rat cardiomyocytes were subjected to hypoxia-reoxygenation in the absence or presence of eEPCs with or without Tβ4 short hairpin RNA (shRNA) transfection. In vivo, pigs (n=9 per group) underwent percutaneous left anterior descending artery occlusion for 60 minutes on day 1. After 55 minutes of ischemia, control eEPCs (5×106 cells) or cells transfected with Tβ4 shRNA when indicated or 15 mg Tβ4 alone were retroinfused into the anterior interventricular vein. Segmental endocardial shortening in the infarct zone at 150-bpm atrial pacing, infarct size (triphenyl tetrazolium chloride viability and m...read more
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In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
Li Qian,Yu Huang,C. Ian Spencer,Amy Foley,Vasanth Vedantham,Lei Liu,Simon J. Conway,Ji-Dong Fu,Deepak Srivastava +8 more
TL;DR: In this article, the authors used genetic lineage tracing to show that resident nonmyocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation.
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Abstract 10466: In Vivo Reprogramming of Murine Cardiac Fibroblasts into Induced Cardiomyocytes
Li Qian,Yu Huang,Amy Foley,Vasanth Vedantham,Ian Spencer,Simon J. Conway,Ji-Dong Fu,Deepak Srivastava +7 more
TL;DR: It is shown that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation and delivery of the pro-angiogenic and fibroblast-activating peptides resulted in further improvements in scar area and cardiac function.
Journal ArticleDOI
Paracrine mechanisms of stem cell reparative and regenerative actions in the heart.
Maria Mirotsou,Tilanthi M. Jayawardena,Jeffrey Schmeckpeper,Massimiliano Gnecchi,Victor J. Dzau +4 more
TL;DR: The potential for diverse stem cell populations to moderate many of the same processes as well as key paracrine factors and molecular pathways involved in stem cell-mediated cardiac repair will be discussed in this review.
Journal ArticleDOI
Inhibition of MicroRNA-92a Protects Against Ischemia/Reperfusion Injury in a Large-Animal Model
Rabea Hinkel,Daniela Penzkofer,Stephanie Zühlke,Ariane Fischer,Wira Husada,Quan-Fu Xu,Elisabeth Baloch,Eva van Rooij,Andreas M. Zeiher,Christian Kupatt,Stefanie Dimmeler +10 more
TL;DR: Regional LNA-92a delivery reduces miR- 92a levels and infarct size and postischemic loss of function and might be a novel therapeutic tool to preserve cardiac function after ischemia.
Journal ArticleDOI
Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition.
Omonigho Aisagbonhi,Meena Rai,Sergey Ryzhov,Nick Atria,Igor Feoktistov,Antonis K. Hatzopoulos +5 more
TL;DR: It is demonstrated that canonical Wnt activation and EndMT are molecular and cellular responses to MI and that canonicalWnt signaling activity is a characteristic property of EndMT-derived mesenchymal cells that take part in cardiac tissue repair after MI.
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