miRNA‐6236 Regulation of Postischemic Skeletal Muscle Angiogenesis
Background Peripheral arterial disease affects >200 million people worldwide and is characterized by impaired blood flow to the lower extremities. There are no effective medical treatments available. Using the mouse hind‐limb ischemia model and miRNA sequencing, we identified a novel miRNA, miR‐6...
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Wiley
2024-12-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.035923 |
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| author | Arul M. Mani Victor Lamin Ronan C. Peach Eli H. Friesen Thomas Wong Madhu V. Singh Ayotunde O. Dokun |
| author_facet | Arul M. Mani Victor Lamin Ronan C. Peach Eli H. Friesen Thomas Wong Madhu V. Singh Ayotunde O. Dokun |
| author_sort | Arul M. Mani |
| collection | DOAJ |
| description | Background Peripheral arterial disease affects >200 million people worldwide and is characterized by impaired blood flow to the lower extremities. There are no effective medical treatments available. Using the mouse hind‐limb ischemia model and miRNA sequencing, we identified a novel miRNA, miR‐6236, whose expression significantly elevated in ischemic mouse limbs compared with nonischemic limbs. The role of miR‐6236 in general or in postischemic angiogenesis is not known. Here we describe its role using in vivo and in vitro models of peripheral arterial disease. Methods and Results In primary mouse and human endothelial cells, we studied the effect of simulated ischemia on miR‐6236 expression and assessed its role in cell viability, apoptosis, migration, and tube formation during ischemia. Furthermore, we developed miR‐6236 null mice and tested its role in postischemic perfusion recovery using the hind‐limb ischemia model. Lastly, using bioinformatics and gene expression analysis, we identified putative angiogenic miR‐6236 targets. In vitro simulated ischemia‐enhanced miR‐6236 expression in mouse and human endothelial cells, whereas its inhibition improved viability, migration, tube formation, and reduced apoptosis. In vivo ischemic mouse skeletal muscle tissue showed higher miR‐6236 expression compared with nonischemic muscles. Loss of miR‐6236 improved impaired postischemic perfusion recovery and poor angiogenesis associated with streptozotocin‐induced diabetes in mice. Six of the 8 miR‐6236 predicted angiogenic target mRNAs showed expression consistent with regulation by miR‐6236 in ischemic skeletal muscle. Conclusions Our results show for the first time that miR‐6236 plays a key role in regulating postischemic perfusion recovery and angiogenesis. |
| format | Article |
| id | doaj-art-97219a33abd14408be23f06bfe1baf85 |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-97219a33abd14408be23f06bfe1baf852024-12-03T10:06:25ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-12-01132310.1161/JAHA.124.035923miRNA‐6236 Regulation of Postischemic Skeletal Muscle AngiogenesisArul M. Mani0Victor Lamin1Ronan C. Peach2Eli H. Friesen3Thomas Wong4Madhu V. Singh5Ayotunde O. Dokun6Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA USADivision of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA USADivision of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA USADivision of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA USADivision of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA USADivision of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA USADivision of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA USABackground Peripheral arterial disease affects >200 million people worldwide and is characterized by impaired blood flow to the lower extremities. There are no effective medical treatments available. Using the mouse hind‐limb ischemia model and miRNA sequencing, we identified a novel miRNA, miR‐6236, whose expression significantly elevated in ischemic mouse limbs compared with nonischemic limbs. The role of miR‐6236 in general or in postischemic angiogenesis is not known. Here we describe its role using in vivo and in vitro models of peripheral arterial disease. Methods and Results In primary mouse and human endothelial cells, we studied the effect of simulated ischemia on miR‐6236 expression and assessed its role in cell viability, apoptosis, migration, and tube formation during ischemia. Furthermore, we developed miR‐6236 null mice and tested its role in postischemic perfusion recovery using the hind‐limb ischemia model. Lastly, using bioinformatics and gene expression analysis, we identified putative angiogenic miR‐6236 targets. In vitro simulated ischemia‐enhanced miR‐6236 expression in mouse and human endothelial cells, whereas its inhibition improved viability, migration, tube formation, and reduced apoptosis. In vivo ischemic mouse skeletal muscle tissue showed higher miR‐6236 expression compared with nonischemic muscles. Loss of miR‐6236 improved impaired postischemic perfusion recovery and poor angiogenesis associated with streptozotocin‐induced diabetes in mice. Six of the 8 miR‐6236 predicted angiogenic target mRNAs showed expression consistent with regulation by miR‐6236 in ischemic skeletal muscle. Conclusions Our results show for the first time that miR‐6236 plays a key role in regulating postischemic perfusion recovery and angiogenesis.https://www.ahajournals.org/doi/10.1161/JAHA.124.035923angiogenesisendothelial cellsischemiamiR‐6236peripheral arterial disease |
| spellingShingle | Arul M. Mani Victor Lamin Ronan C. Peach Eli H. Friesen Thomas Wong Madhu V. Singh Ayotunde O. Dokun miRNA‐6236 Regulation of Postischemic Skeletal Muscle Angiogenesis Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiogenesis endothelial cells ischemia miR‐6236 peripheral arterial disease |
| title | miRNA‐6236 Regulation of Postischemic Skeletal Muscle Angiogenesis |
| title_full | miRNA‐6236 Regulation of Postischemic Skeletal Muscle Angiogenesis |
| title_fullStr | miRNA‐6236 Regulation of Postischemic Skeletal Muscle Angiogenesis |
| title_full_unstemmed | miRNA‐6236 Regulation of Postischemic Skeletal Muscle Angiogenesis |
| title_short | miRNA‐6236 Regulation of Postischemic Skeletal Muscle Angiogenesis |
| title_sort | mirna 6236 regulation of postischemic skeletal muscle angiogenesis |
| topic | angiogenesis endothelial cells ischemia miR‐6236 peripheral arterial disease |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.035923 |
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