Prolyl Hydroxylase Domain Protein 2 Silencing Enhances the Survival and Paracrine Function of Transplanted Adipose-Derived Stem Cells in Infarcted Myocardium
- 19 July 2013
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 113 (3), 288-300
- https://doi.org/10.1161/circresaha.113.300929
Abstract
Rationale:Transplantation of stem cells into damaged hearts has had modest success as a treatment for ischemic heart disease. One of the limitations is the poor stem cell survival in the diseased microenvironment. Prolyl hydroxylase domain protein 2 (PHD2) is a cellular oxygen sensor that regulates 2 key transcription factors involved in cell survival and inflammation: hypoxia-inducible factor and nuclear factor-κB. Objective:We studied whether and how PHD2 silencing in human adipose-derived stem cells (ADSCs) enhances their cardioprotective effects after transplantation into infarcted hearts. Methods and Results:ADSCs were transduced with lentiviral short hairpin RNA against prolyl hydroxylase domain protein 2 (shPHD2) to silence PHD2. ADSCs, with or without shPHD2, were transplanted after myocardial infarction in mice. ADSCs reduced cardiomyocyte apoptosis, fibrosis, and infarct size and improved cardiac function. shPHD2-ADSCs exerted significantly more protection. PHD2 silencing induced greater ADSC su...Keywords
This publication has 39 references indexed in Scilit:
- HIF1α is required for survival maintenance of chronic myeloid leukemia stem cellsBlood, 2012
- Noncanonical NF-κB Signaling Regulates Hematopoietic Stem Cell Self-Renewal and Microenvironment InteractionsThe International Journal of Cell Cloning, 2012
- Potent endothelial progenitor cell-conditioned media-related anti-apoptotic, cardiotrophic, and pro-angiogenic effects post-myocardial infarction are mediated by insulin-like growth factor-1European Heart Journal, 2011
- Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failureBlood, 2008
- Human mesenchymal stem cells stimulated by TNF-α, LPS, or hypoxia produce growth factors by an NFκB- but not JNK-dependent mechanismAmerican Journal of Physiology-Cell Physiology, 2008
- Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarctionEuropean Heart Journal, 2007
- Lack of Hypoxia-Inducible Factor-1α Impairs Midbrain Neural Precursor Cells Involving Vascular Endothelial Growth Factor SignalingJournal of Neuroscience, 2007
- Prolyl hydroxylase-1 negatively regulates IκB kinase-β, giving insight into hypoxia-induced NFκB activityProceedings of the National Academy of Sciences of the United States of America, 2006
- HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1 in normoxiaThe EMBO Journal, 2003
- In Cardiomyocyte Hypoxia, Insulin-Like Growth Factor-I-Induced Antiapoptotic Signaling Requires Phosphatidylinositol-3-OH-Kinase-Dependent and Mitogen-Activated Protein Kinase-Dependent Activation of the Transcription Factor cAMP Response Element-Binding ProteinCirculation, 2001