Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart
Summary: Vascular endothelial growth factor B (VEGF-B) is an interesting therapeutic candidate for coronary artery disease. However, it can also cause ventricular arrhythmias, potentially preventing its use in clinics. We cloned VEGF-B isoforms with different receptor binding profiles to clarify the...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221015042 |
| _version_ | 1819095286501343232 |
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| author | Henna Korpela Olli-Pekka Hätinen Tiina Nieminen Rahul Mallick Pyry Toivanen Jonna Airaksinen Kaisa Valli Mikko Hakulinen Pekka Poutiainen Jussi Nurro Seppo Ylä-Herttuala |
| author_facet | Henna Korpela Olli-Pekka Hätinen Tiina Nieminen Rahul Mallick Pyry Toivanen Jonna Airaksinen Kaisa Valli Mikko Hakulinen Pekka Poutiainen Jussi Nurro Seppo Ylä-Herttuala |
| author_sort | Henna Korpela |
| collection | DOAJ |
| description | Summary: Vascular endothelial growth factor B (VEGF-B) is an interesting therapeutic candidate for coronary artery disease. However, it can also cause ventricular arrhythmias, potentially preventing its use in clinics. We cloned VEGF-B isoforms with different receptor binding profiles to clarify the roles of VEGFR-1 and Nrp-1 in angiogenesis and to see if angiogenic properties can be maintained while avoiding side effects. VEGF-B constructs were studied in vivo using adenovirus (Ad)-mediated intramyocardial gene transfers into the normoxic and ischemic porcine heart (n = 51). It was found that the unprocessed isoform VEGF-B186R127S is as efficient angiogenic growth factor as the native VEGF-B186 in normoxic and ischemic heart. In addition, AdVEGF-B186R127S increased myocardial perfusion reserve by 22% in ischemic heart without any side effects. AdVEGF-B127 (VEGFR-1 and Nrp-1 ligand) and AdVEGF-B109 (VEGFR-1 ligand) did not induce angiogenesis. Thus, VEGF-B186 is angiogenic only before its proteolytic processing to VEGF-B127. Only the VEGF-B186 C-terminal fragment was associated with arrhythmias. |
| first_indexed | 2024-12-21T23:40:53Z |
| format | Article |
| id | doaj.art-b15e0250c9894d889ee8b3933a4498ad |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-21T23:40:53Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b15e0250c9894d889ee8b3933a4498ad2022-12-21T18:46:14ZengElsevieriScience2589-00422021-12-012412103533Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heartHenna Korpela0Olli-Pekka Hätinen1Tiina Nieminen2Rahul Mallick3Pyry Toivanen4Jonna Airaksinen5Kaisa Valli6Mikko Hakulinen7Pekka Poutiainen8Jussi Nurro9Seppo Ylä-Herttuala10A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland; Kuopio Center for Gene and Cell Therapy, Kuopio, FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandKuopio University Hospital, Kuopio, FinlandKuopio University Hospital, Kuopio, FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandA.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland; Heart Center and Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland; Corresponding authorSummary: Vascular endothelial growth factor B (VEGF-B) is an interesting therapeutic candidate for coronary artery disease. However, it can also cause ventricular arrhythmias, potentially preventing its use in clinics. We cloned VEGF-B isoforms with different receptor binding profiles to clarify the roles of VEGFR-1 and Nrp-1 in angiogenesis and to see if angiogenic properties can be maintained while avoiding side effects. VEGF-B constructs were studied in vivo using adenovirus (Ad)-mediated intramyocardial gene transfers into the normoxic and ischemic porcine heart (n = 51). It was found that the unprocessed isoform VEGF-B186R127S is as efficient angiogenic growth factor as the native VEGF-B186 in normoxic and ischemic heart. In addition, AdVEGF-B186R127S increased myocardial perfusion reserve by 22% in ischemic heart without any side effects. AdVEGF-B127 (VEGFR-1 and Nrp-1 ligand) and AdVEGF-B109 (VEGFR-1 ligand) did not induce angiogenesis. Thus, VEGF-B186 is angiogenic only before its proteolytic processing to VEGF-B127. Only the VEGF-B186 C-terminal fragment was associated with arrhythmias.http://www.sciencedirect.com/science/article/pii/S2589004221015042Cellular therapyBiochemistryMolecular biology |
| spellingShingle | Henna Korpela Olli-Pekka Hätinen Tiina Nieminen Rahul Mallick Pyry Toivanen Jonna Airaksinen Kaisa Valli Mikko Hakulinen Pekka Poutiainen Jussi Nurro Seppo Ylä-Herttuala Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart iScience Cellular therapy Biochemistry Molecular biology |
| title | Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart |
| title_full | Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart |
| title_fullStr | Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart |
| title_full_unstemmed | Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart |
| title_short | Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart |
| title_sort | adenoviral vegf b186r127s gene transfer induces angiogenesis and improves perfusion in ischemic heart |
| topic | Cellular therapy Biochemistry Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221015042 |
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