Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice.
"Epigenetherapy" alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model. shRNA complementary to the promoter of va...
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2014
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oai:doaj.org-article:99c378ad6db04a1ba9c9b3aeb17d77fc2021-11-18T08:30:49ZEpigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice.1932-620310.1371/journal.pone.0089979https://doaj.org/article/99c378ad6db04a1ba9c9b3aeb17d77fc2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587164/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203"Epigenetherapy" alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model. shRNA complementary to the promoter of vascular endothelial growth factor (VEGF-A) was able to upregulate endogenous VEGF-A expression. Histological and multiphoton microscope analysis confirmed the therapeutic effect in the transduced hearts. Magnetic resonance imaging (MRI) showed in vivo that the infarct size was significantly reduced in the treatment group 14 days after the epigenetherapy. Importantly, we show that promoter-targeted shRNA upregulates all isoforms of endogenous VEGF-A and that an intact hairpin structure is required for the shRNA activity. In conclusion, regulation of gene expression at the promoter level is a promising new treatment strategy for myocardial infarction and also potentially useful for the upregulation of other endogenous genes.Mikko P TurunenTiia HussoHaja MusthafaSvetlana LaidinenGalina DragnevaNihay Laham-KaramSanna HonkanenAnne PaakinahoJohanna P LaakkonenErhe GaoMaija Vihinen-RantaTimo LiimatainenSeppo Ylä-HerttualaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89979 (2014) |
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Medicine R Science Q Mikko P Turunen Tiia Husso Haja Musthafa Svetlana Laidinen Galina Dragneva Nihay Laham-Karam Sanna Honkanen Anne Paakinaho Johanna P Laakkonen Erhe Gao Maija Vihinen-Ranta Timo Liimatainen Seppo Ylä-Herttuala Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice. |
| description |
"Epigenetherapy" alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model. shRNA complementary to the promoter of vascular endothelial growth factor (VEGF-A) was able to upregulate endogenous VEGF-A expression. Histological and multiphoton microscope analysis confirmed the therapeutic effect in the transduced hearts. Magnetic resonance imaging (MRI) showed in vivo that the infarct size was significantly reduced in the treatment group 14 days after the epigenetherapy. Importantly, we show that promoter-targeted shRNA upregulates all isoforms of endogenous VEGF-A and that an intact hairpin structure is required for the shRNA activity. In conclusion, regulation of gene expression at the promoter level is a promising new treatment strategy for myocardial infarction and also potentially useful for the upregulation of other endogenous genes. |
| format |
article |
| author |
Mikko P Turunen Tiia Husso Haja Musthafa Svetlana Laidinen Galina Dragneva Nihay Laham-Karam Sanna Honkanen Anne Paakinaho Johanna P Laakkonen Erhe Gao Maija Vihinen-Ranta Timo Liimatainen Seppo Ylä-Herttuala |
| author_facet |
Mikko P Turunen Tiia Husso Haja Musthafa Svetlana Laidinen Galina Dragneva Nihay Laham-Karam Sanna Honkanen Anne Paakinaho Johanna P Laakkonen Erhe Gao Maija Vihinen-Ranta Timo Liimatainen Seppo Ylä-Herttuala |
| author_sort |
Mikko P Turunen |
| title |
Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice. |
| title_short |
Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice. |
| title_full |
Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice. |
| title_fullStr |
Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice. |
| title_full_unstemmed |
Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice. |
| title_sort |
epigenetic upregulation of endogenous vegf-a reduces myocardial infarct size in mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/99c378ad6db04a1ba9c9b3aeb17d77fc |
| work_keys_str_mv |
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| _version_ |
1718421699090710528 |