Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6
Background/Aims: Endothelial cell injury and subsequent death play an essential role in the pathogenesis of atherosclerosis. Autophagy of endothelial cells has a protective role against development of atherosclerosis, whereas the molecular regulation of endothelial cell autophagy is unclear. MicroRN...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-10-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/430402 |
| _version_ | 1818855663875391488 |
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| author | Tao Zhang Feng Tian Jing Wang Jing Jing Shan-Shan Zhou Yun-Dai Chen |
| author_facet | Tao Zhang Feng Tian Jing Wang Jing Jing Shan-Shan Zhou Yun-Dai Chen |
| author_sort | Tao Zhang |
| collection | DOAJ |
| description | Background/Aims: Endothelial cell injury and subsequent death play an essential role in the pathogenesis of atherosclerosis. Autophagy of endothelial cells has a protective role against development of atherosclerosis, whereas the molecular regulation of endothelial cell autophagy is unclear. MicroRNA-30 (miR-30) is a known autophagy suppressor in some biological processes, while it is unknown whether this regulatory axis may be similarly involved in the development of atherosclerosis. Here, we aimed to answer these questions in the current study. Methods: We examined the levels of endothelial cell autophagy in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of autophagy-associated protein 6 (ATG6, or Beclin-1) and the levels of miR-30 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-30 and 3'-UTR of ATG6 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-30 were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). Results: HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as NOR mice) did not. Compared to NOR mice, HFD mice had significantly lower levels of endothelial cell autophagy, resulting from decreases in ATG6 protein, but not mRNA. The decreases in ATG6 in endothelial cells were due to HFD-induced increases in miR-30, which suppressed the translation of ATG6 mRNA via 3′-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Conclusion: Upregulation of miR-30 by HFD may impair the protective effects of endothelial cell autophagy against development of atherosclerosis through suppressing protein translation of ATG6. |
| first_indexed | 2024-12-19T08:12:11Z |
| format | Article |
| id | doaj.art-c693eb5d3c6c4fc9bd541866d624962b |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-19T08:12:11Z |
| publishDate | 2015-10-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-c693eb5d3c6c4fc9bd541866d624962b2022-12-21T20:29:35ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-10-013741369137810.1159/000430402430402Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6Tao ZhangFeng TianJing WangJing JingShan-Shan ZhouYun-Dai ChenBackground/Aims: Endothelial cell injury and subsequent death play an essential role in the pathogenesis of atherosclerosis. Autophagy of endothelial cells has a protective role against development of atherosclerosis, whereas the molecular regulation of endothelial cell autophagy is unclear. MicroRNA-30 (miR-30) is a known autophagy suppressor in some biological processes, while it is unknown whether this regulatory axis may be similarly involved in the development of atherosclerosis. Here, we aimed to answer these questions in the current study. Methods: We examined the levels of endothelial cell autophagy in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of autophagy-associated protein 6 (ATG6, or Beclin-1) and the levels of miR-30 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-30 and 3'-UTR of ATG6 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-30 were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). Results: HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as NOR mice) did not. Compared to NOR mice, HFD mice had significantly lower levels of endothelial cell autophagy, resulting from decreases in ATG6 protein, but not mRNA. The decreases in ATG6 in endothelial cells were due to HFD-induced increases in miR-30, which suppressed the translation of ATG6 mRNA via 3′-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Conclusion: Upregulation of miR-30 by HFD may impair the protective effects of endothelial cell autophagy against development of atherosclerosis through suppressing protein translation of ATG6.http://www.karger.com/Article/FullText/430402AtherosclerosisEndothelial cell autophagyApoE (-/-)High fat diet (HFD)ox-LDLATG6miR-30 |
| spellingShingle | Tao Zhang Feng Tian Jing Wang Jing Jing Shan-Shan Zhou Yun-Dai Chen Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6 Cellular Physiology and Biochemistry Atherosclerosis Endothelial cell autophagy ApoE (-/-) High fat diet (HFD) ox-LDL ATG6 miR-30 |
| title | Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6 |
| title_full | Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6 |
| title_fullStr | Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6 |
| title_full_unstemmed | Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6 |
| title_short | Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6 |
| title_sort | endothelial cell autophagy in atherosclerosis is regulated by mir 30 mediated translational control of atg6 |
| topic | Atherosclerosis Endothelial cell autophagy ApoE (-/-) High fat diet (HFD) ox-LDL ATG6 miR-30 |
| url | http://www.karger.com/Article/FullText/430402 |
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