Shock Wave Therapy Enhances Angiogenesis through VEGFR2 Activation and Recycling
Abstract Although low-energy shock wave (SW) is adopted to treat ischemic diseases because of its pro-angiogenic properties, the underlying mechanism remains unclear. This study is aimed at testing whether SW-induced angiogenesis may be through endothelial vascular endothelial growth factor receptor...
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| Format: | Article |
| Language: | English |
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BMC
2016-12-01
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| Series: | Molecular Medicine |
| Online Access: | http://link.springer.com/article/10.2119/molmed.2016.00108 |
| _version_ | 1817976085643526144 |
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| author | Tien-Hung Huang Cheuk-Kwan Sun Yi-Ling Chen Ching-Jen Wang Tsung-Cheng Yin Mel S Lee Hon-Kan Yip |
| author_facet | Tien-Hung Huang Cheuk-Kwan Sun Yi-Ling Chen Ching-Jen Wang Tsung-Cheng Yin Mel S Lee Hon-Kan Yip |
| author_sort | Tien-Hung Huang |
| collection | DOAJ |
| description | Abstract Although low-energy shock wave (SW) is adopted to treat ischemic diseases because of its pro-angiogenic properties, the underlying mechanism remains unclear. This study is aimed at testing whether SW-induced angiogenesis may be through endothelial vascular endothelial growth factor receptor 2 (VEGFR2) signaling and trafficking. Phosphorylation of VEGFR2-Akt-eNOS axis and production of nitric oxide (NO) were determined in human umbilical vein endothelial cells (HUVECs) treated with SW. Carotid artery in ob/ob mice was treated with SW before evaluation with sprouting assay. Critical limb ischemia was induced in ob/ob mice to evaluate blood flow recovery post-SW treatment. Tube formation and migration assays were also performed with/without SW treatment in the presence/absence of SU5416 (VEGFR2 kinase inhibitor) and siRNA-driven silencing of VEGFR2. Chloroquine was used for disrupting endosome, and Rab11a controlling slow endocytic recycling was silenced with siRNA in vitro. Following SW treatment, augmented ligand-independent phosphorylation in VEGFR2-Akt-eNOS axis and endogenous NO production, increased cellular migration and tube formation and elevated sprouting of carotid artery and blood flow in ischemic limb in ob/ob mice were noted. Moreover, SU5416 and VEGFR2 silencing both inhibited SW-induced angiogenesis. SW-induced angiogenesis, accompanied by increased VEGFR2 protein expression without transcriptional change, was suppressed by chloroquine and Rab11a silencing. We concluded that SW enhanced angiogenesis via ligand-independent activation of VEGFR2 and further prolonged angiogenesis through endosome-to-plasma membrane recycling in endothelial cells. |
| first_indexed | 2024-04-13T21:57:53Z |
| format | Article |
| id | doaj.art-f022f3e0695844748ef54a2a03c62d79 |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-04-13T21:57:53Z |
| publishDate | 2016-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-f022f3e0695844748ef54a2a03c62d792022-12-22T02:28:12ZengBMCMolecular Medicine1076-15511528-36582016-12-0122185086210.2119/molmed.2016.00108Shock Wave Therapy Enhances Angiogenesis through VEGFR2 Activation and RecyclingTien-Hung Huang0Cheuk-Kwan Sun1Yi-Ling Chen2Ching-Jen Wang3Tsung-Cheng Yin4Mel S Lee5Hon-Kan Yip6Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalDepartment of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International StudentDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalCenter for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial HospitalDepartment of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial HospitalAbstract Although low-energy shock wave (SW) is adopted to treat ischemic diseases because of its pro-angiogenic properties, the underlying mechanism remains unclear. This study is aimed at testing whether SW-induced angiogenesis may be through endothelial vascular endothelial growth factor receptor 2 (VEGFR2) signaling and trafficking. Phosphorylation of VEGFR2-Akt-eNOS axis and production of nitric oxide (NO) were determined in human umbilical vein endothelial cells (HUVECs) treated with SW. Carotid artery in ob/ob mice was treated with SW before evaluation with sprouting assay. Critical limb ischemia was induced in ob/ob mice to evaluate blood flow recovery post-SW treatment. Tube formation and migration assays were also performed with/without SW treatment in the presence/absence of SU5416 (VEGFR2 kinase inhibitor) and siRNA-driven silencing of VEGFR2. Chloroquine was used for disrupting endosome, and Rab11a controlling slow endocytic recycling was silenced with siRNA in vitro. Following SW treatment, augmented ligand-independent phosphorylation in VEGFR2-Akt-eNOS axis and endogenous NO production, increased cellular migration and tube formation and elevated sprouting of carotid artery and blood flow in ischemic limb in ob/ob mice were noted. Moreover, SU5416 and VEGFR2 silencing both inhibited SW-induced angiogenesis. SW-induced angiogenesis, accompanied by increased VEGFR2 protein expression without transcriptional change, was suppressed by chloroquine and Rab11a silencing. We concluded that SW enhanced angiogenesis via ligand-independent activation of VEGFR2 and further prolonged angiogenesis through endosome-to-plasma membrane recycling in endothelial cells.http://link.springer.com/article/10.2119/molmed.2016.00108 |
| spellingShingle | Tien-Hung Huang Cheuk-Kwan Sun Yi-Ling Chen Ching-Jen Wang Tsung-Cheng Yin Mel S Lee Hon-Kan Yip Shock Wave Therapy Enhances Angiogenesis through VEGFR2 Activation and Recycling Molecular Medicine |
| title | Shock Wave Therapy Enhances Angiogenesis through VEGFR2 Activation and Recycling |
| title_full | Shock Wave Therapy Enhances Angiogenesis through VEGFR2 Activation and Recycling |
| title_fullStr | Shock Wave Therapy Enhances Angiogenesis through VEGFR2 Activation and Recycling |
| title_full_unstemmed | Shock Wave Therapy Enhances Angiogenesis through VEGFR2 Activation and Recycling |
| title_short | Shock Wave Therapy Enhances Angiogenesis through VEGFR2 Activation and Recycling |
| title_sort | shock wave therapy enhances angiogenesis through vegfr2 activation and recycling |
| url | http://link.springer.com/article/10.2119/molmed.2016.00108 |
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