Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation
Objective: Advanced age is associated with impaired angiogenesis in part because of mitochondrial dysfunction. We have recently reported that leonurine exerts protective effects in neuron via regulation of mitochondrial function. The aim of this study was to explore whether leonurine is able to atte...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00284/full |
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| author | Jia Qi Jia Qi Jing J. Wang Jun L. Duan Zhao Y. Lu Yang G. Yuan |
| author_facet | Jia Qi Jia Qi Jing J. Wang Jun L. Duan Zhao Y. Lu Yang G. Yuan |
| author_sort | Jia Qi |
| collection | DOAJ |
| description | Objective: Advanced age is associated with impaired angiogenesis in part because of mitochondrial dysfunction. We have recently reported that leonurine exerts protective effects in neuron via regulation of mitochondrial function. The aim of this study was to explore whether leonurine is able to attenuate mitochondrial dysfunction and to enhance angiogenesis in old rats with hindlimb ischemia.Methods and Results: At day 14 after surgery, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression was decreased in the ischemic muscle of aged animals, which was accompanied by enhanced oxidative stress, increased mitochondrial damage, decreased capillary density, and reduced limb perfusion compared with young mice. Importantly, these effects were inhibited by leonurine treatment in old animals. In vitro, we showed that the functional activities (migration and tube formation) of human umbilical vein endothelial cells (HUVECs) were significantly impaired in senescent compared to young. However, leonurine rescued HUVECs functional activities in senescent HUVECs. Mechanistically, we found that leonurine restored the age-dependent reduction in HIF activity and subsequent reduced VEGF expression in senescent HUVECs. Moreover, the mitochondrial oxidative stress was significantly augmented in senescent HUVECs, in association with reduced mitochondrial function. However, leonurine significantly reduced the mitochondrial oxidative stress and restored the mitochondrial membrane potential.Conclusion: Our results demonstrate that leonurine protects against age-dependent impairment of angiogenesis possibly through attenuation of mitochondrial dysfunction and subsequent VEGF up-regulation impairment. |
| first_indexed | 2024-12-14T09:56:37Z |
| format | Article |
| id | doaj.art-8a13e36e00cc47d9845f1cab67a62f01 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T09:56:37Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-8a13e36e00cc47d9845f1cab67a62f012022-12-21T23:07:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-06-01810.3389/fphar.2017.00284251793Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF ActivationJia Qi0Jia Qi1Jing J. Wang2Jun L. Duan3Zhao Y. Lu4Yang G. Yuan5Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiaotong UniversityShanghai, ChinaDepartment of Gerontology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong UniversityShanghai, ChinaDepartment of Nephrology, School of Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiaotong UniversityShanghai, ChinaDepartment of Gerontology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong UniversityShanghai, ChinaDepartment of Gerontology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong UniversityShanghai, ChinaDepartment of Nephrology, The First affiliated Hospital of Nanjing Medical UniversityNanjing, ChinaObjective: Advanced age is associated with impaired angiogenesis in part because of mitochondrial dysfunction. We have recently reported that leonurine exerts protective effects in neuron via regulation of mitochondrial function. The aim of this study was to explore whether leonurine is able to attenuate mitochondrial dysfunction and to enhance angiogenesis in old rats with hindlimb ischemia.Methods and Results: At day 14 after surgery, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression was decreased in the ischemic muscle of aged animals, which was accompanied by enhanced oxidative stress, increased mitochondrial damage, decreased capillary density, and reduced limb perfusion compared with young mice. Importantly, these effects were inhibited by leonurine treatment in old animals. In vitro, we showed that the functional activities (migration and tube formation) of human umbilical vein endothelial cells (HUVECs) were significantly impaired in senescent compared to young. However, leonurine rescued HUVECs functional activities in senescent HUVECs. Mechanistically, we found that leonurine restored the age-dependent reduction in HIF activity and subsequent reduced VEGF expression in senescent HUVECs. Moreover, the mitochondrial oxidative stress was significantly augmented in senescent HUVECs, in association with reduced mitochondrial function. However, leonurine significantly reduced the mitochondrial oxidative stress and restored the mitochondrial membrane potential.Conclusion: Our results demonstrate that leonurine protects against age-dependent impairment of angiogenesis possibly through attenuation of mitochondrial dysfunction and subsequent VEGF up-regulation impairment.http://journal.frontiersin.org/article/10.3389/fphar.2017.00284/fullleonurinemitochondrial dysfunctionangiogenesishindlimb ischemiaage |
| spellingShingle | Jia Qi Jia Qi Jing J. Wang Jun L. Duan Zhao Y. Lu Yang G. Yuan Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation Frontiers in Pharmacology leonurine mitochondrial dysfunction angiogenesis hindlimb ischemia age |
| title | Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation |
| title_full | Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation |
| title_fullStr | Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation |
| title_full_unstemmed | Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation |
| title_short | Leonurine Improves Age-Dependent Impaired Angiogenesis: Possible Involvement of Mitochondrial Function and HIF-1α Dependent VEGF Activation |
| title_sort | leonurine improves age dependent impaired angiogenesis possible involvement of mitochondrial function and hif 1α dependent vegf activation |
| topic | leonurine mitochondrial dysfunction angiogenesis hindlimb ischemia age |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00284/full |
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