E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model
The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Cardiovascular Therapeutics |
| Online Access: | http://dx.doi.org/10.1155/2023/6679390 |
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| author | Antoine J. Ribieras Yulexi Y. Ortiz Yan Li Nga T. Le Carlos T. Huerta Francesca A. Voza Hongwei Shao Roberto I. Vazquez-Padron Zhao-Jun Liu Omaida C. Velazquez |
| author_facet | Antoine J. Ribieras Yulexi Y. Ortiz Yan Li Nga T. Le Carlos T. Huerta Francesca A. Voza Hongwei Shao Roberto I. Vazquez-Padron Zhao-Jun Liu Omaida C. Velazquez |
| author_sort | Antoine J. Ribieras |
| collection | DOAJ |
| description | The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule that mediates cell recruitment during neovascularization. Therapeutic priming of ischemic limb tissues with intramuscular E-selectin gene therapy promotes angiogenesis and reduces tissue loss in a murine hindlimb gangrene model. In this study, we evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. C57BL/6J mice were treated with intramuscular E-selectin/adeno-associated virus serotype 2/2 gene therapy (E-sel/AAV) or LacZ/AAV2/2 (LacZ/AAV) as control and then subjected to femoral artery coagulation. Recovery of hindlimb perfusion was assessed by laser Doppler perfusion imaging and muscle function by treadmill exhaustion and grip strength testing. After three postoperative weeks, hindlimb muscle was harvested for immunofluorescence analysis. At all postoperative time points, mice treated with E-sel/AAV had improved hindlimb perfusion and exercise capacity. E-sel/AAV gene therapy also increased the coexpression of MyoD and Ki-67 in skeletal muscle progenitors and the proportion of Myh7+ myofibers. Altogether, our findings demonstrate that in addition to improving reperfusion, intramuscular E-sel/AAV gene therapy enhances the regeneration of ischemic skeletal muscle with a corresponding benefit on exercise performance. These results suggest a potential role for E-sel/AAV gene therapy as a nonsurgical adjunct in patients with life-limiting PAD. |
| format | Article |
| id | doaj-art-cf5d145b17fa4af49a832cc255517a45 |
| institution | Kabale University |
| issn | 1755-5922 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cardiovascular Therapeutics |
| spelling | doaj-art-cf5d145b17fa4af49a832cc255517a452025-02-03T05:44:21ZengWileyCardiovascular Therapeutics1755-59222023-01-01202310.1155/2023/6679390E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia ModelAntoine J. Ribieras0Yulexi Y. Ortiz1Yan Li2Nga T. Le3Carlos T. Huerta4Francesca A. Voza5Hongwei Shao6Roberto I. Vazquez-Padron7Zhao-Jun Liu8Omaida C. Velazquez9Division of Vascular SurgeryDivision of Vascular SurgeryDivision of Vascular SurgeryDivision of Vascular SurgeryDivision of Vascular SurgeryDivision of Vascular SurgeryDivision of Vascular SurgeryDivision of Vascular SurgeryDivision of Vascular SurgeryDivision of Vascular SurgeryThe response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule that mediates cell recruitment during neovascularization. Therapeutic priming of ischemic limb tissues with intramuscular E-selectin gene therapy promotes angiogenesis and reduces tissue loss in a murine hindlimb gangrene model. In this study, we evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. C57BL/6J mice were treated with intramuscular E-selectin/adeno-associated virus serotype 2/2 gene therapy (E-sel/AAV) or LacZ/AAV2/2 (LacZ/AAV) as control and then subjected to femoral artery coagulation. Recovery of hindlimb perfusion was assessed by laser Doppler perfusion imaging and muscle function by treadmill exhaustion and grip strength testing. After three postoperative weeks, hindlimb muscle was harvested for immunofluorescence analysis. At all postoperative time points, mice treated with E-sel/AAV had improved hindlimb perfusion and exercise capacity. E-sel/AAV gene therapy also increased the coexpression of MyoD and Ki-67 in skeletal muscle progenitors and the proportion of Myh7+ myofibers. Altogether, our findings demonstrate that in addition to improving reperfusion, intramuscular E-sel/AAV gene therapy enhances the regeneration of ischemic skeletal muscle with a corresponding benefit on exercise performance. These results suggest a potential role for E-sel/AAV gene therapy as a nonsurgical adjunct in patients with life-limiting PAD.http://dx.doi.org/10.1155/2023/6679390 |
| spellingShingle | Antoine J. Ribieras Yulexi Y. Ortiz Yan Li Nga T. Le Carlos T. Huerta Francesca A. Voza Hongwei Shao Roberto I. Vazquez-Padron Zhao-Jun Liu Omaida C. Velazquez E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model Cardiovascular Therapeutics |
| title | E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model |
| title_full | E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model |
| title_fullStr | E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model |
| title_full_unstemmed | E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model |
| title_short | E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model |
| title_sort | e selectin aav gene therapy promotes myogenesis and skeletal muscle recovery in a mouse hindlimb ischemia model |
| url | http://dx.doi.org/10.1155/2023/6679390 |
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