Prolyl Hydroxylase Domain Protein 2 Silencing Enhances the Survival and Paracrine Function of Transplanted Adipose-Derived Stem Cells in Infarcted Myocardium

• DOI: 10.1161/circresaha.113.300929
• Publication Date: 2013-05-22T05:04:27Z
• Authors: Wei Eric Wang; Dezhong Yang; Liangpeng Li; Wei Wang; Yulan Peng; Caiyu Chen; Peng Chen; Xuewei Xia; Hongyong Wang; Jiahui Jiang; Qiao Liao; Yuan Li; Ganfeng Xie; Haiyun Huang; Yanli Guo; Linda Ye; Dayue Darrel Duan; Xiongwen Chen; Steven R. Houser; Chunyu Zeng
• Keywords: Male; Cell Survival; Myocardial Infarction; Procollagen-Proline Dioxygenase; 3. Good health; Hypoxia-Inducible Factor-Proline Dioxygenases; Mice, Inbred C57BL; Mice; Adipose Tissue; Paracrine Communication; Animals; Humans; Gene Silencing; RNA, Small Interfering; Cells, Cultured; Stem Cell Transplantation

Transplantation of stem cells into damaged hearts has had modest success as a treatment for ischemic heart disease. One the limitations is poor cell survival in diseased microenvironment. Prolyl hydroxylase domain protein 2 (PHD2) cellular oxygen sensor that regulates key transcription factors involved and inflammation: hypoxia-inducible factor nuclear factor-κB.We studied whether how PHD2 silencing human adipose-derived (ADSCs) enhances their cardioprotective effects after transplantation infarcted hearts.ADSCs were transduced with lentiviral short hairpin RNA against prolyl (shPHD2) to silence PHD2. ADSCs, or without shPHD2, transplanted myocardial infarction mice. ADSCs reduced cardiomyocyte apoptosis, fibrosis, infarct size improved cardiac function. shPHD2-ADSCs exerted significantly more protection. induced greater ADSC survival, which was abolished by factor-1α. Conditioned medium from decreased apoptosis. Insulin-like growth factor-1 (IGF-1) levels higher conditioned versus depletion IGF-1 attenuated shPHD2-ADSC-conditioned medium. Nuclear factor-κB activation shPHD2 induce secretion via binding gene promoter.PHD2 promotes paracrine function protect cardiomyocytes. The prosurvival effect on factor-1α dependent, enhanced associated factor-κB-mediated upregulation. may be novel strategy enhancing effectiveness therapy infarction.