MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis
Background: The impairment of endothelial cells triggered by oxidized low-density lipoprotein (ox-LDL) stands as a critical event in the advancement of atherosclerosis (AS). MiR-497-5p has been recognized as a potential predictor for AS, but its precise involvement in ox-LDL-induced endothelial cell...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024049181 |
| _version_ | 1797221741865467904 |
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| author | Wei Lu Guoqing Wan He Zhu Tao Zhu Xinmei Zhang |
| author_facet | Wei Lu Guoqing Wan He Zhu Tao Zhu Xinmei Zhang |
| author_sort | Wei Lu |
| collection | DOAJ |
| description | Background: The impairment of endothelial cells triggered by oxidized low-density lipoprotein (ox-LDL) stands as a critical event in the advancement of atherosclerosis (AS). MiR-497-5p has been recognized as a potential predictor for AS, but its precise involvement in ox-LDL-induced endothelial cell dysfunction remains to be elucidated. Methods: An in vitro AS cell model was established by exposing human umbilical vein endothelial cells (HUVECs) to 100 μg/mL ox-LDL for 24 h. The assessment of endothelial cell function included evaluating cell viability, caspase-3 activity, inflammatory factors, and oxidative markers. Molecular mechanisms were elucidated through quantitative real-time PCR, Western blot analysis, and luciferase reporter assays. Results: Our investigation revealed that exposure to ox-LDL led to an upregulation in miR-497-5p and p-p38 levels, while downregulating the expression of vascular endothelial growth factor A (VEGFA) and phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) in HUVECs. Ox-LDL exposure resulted in decreased cell viability and angiogenic capacity, coupled with increased apoptosis, inflammation, and oxidative stress in HUVECs, partially mediated by the upregulation of miR-497-5p. We confirmed VEGFA as a direct target of miR-497-5p. Interfering with VEGFA expression significantly reversed the effects mediated by miR-497-5p silencing in HUVECs exposed to ox-LDL. Conclusions: In summary, our findings demonstrate that miR-497-5p exacerbates ox-LDL-induced dysfunction in HUVECs through the activation of the p38/MAPK pathway, mediated by the targeting of VEGFA. |
| first_indexed | 2024-04-24T13:10:16Z |
| format | Article |
| id | doaj.art-11ac48d2640b4763b1d978213003a8d7 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:10:16Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-11ac48d2640b4763b1d978213003a8d72024-04-05T04:41:14ZengElsevierHeliyon2405-84402024-04-01107e28887MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosisWei Lu0Guoqing Wan1He Zhu2Tao Zhu3Xinmei Zhang4Department of Cardiovascular Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, 324000, ChinaSchool of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, ChinaZhejiang Chinese Medical University, Zhejiang, ChinaZhejiang Chinese Medical University, Zhejiang, ChinaDepartment of Cardiovascular Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, 324000, China; Corresponding author.Background: The impairment of endothelial cells triggered by oxidized low-density lipoprotein (ox-LDL) stands as a critical event in the advancement of atherosclerosis (AS). MiR-497-5p has been recognized as a potential predictor for AS, but its precise involvement in ox-LDL-induced endothelial cell dysfunction remains to be elucidated. Methods: An in vitro AS cell model was established by exposing human umbilical vein endothelial cells (HUVECs) to 100 μg/mL ox-LDL for 24 h. The assessment of endothelial cell function included evaluating cell viability, caspase-3 activity, inflammatory factors, and oxidative markers. Molecular mechanisms were elucidated through quantitative real-time PCR, Western blot analysis, and luciferase reporter assays. Results: Our investigation revealed that exposure to ox-LDL led to an upregulation in miR-497-5p and p-p38 levels, while downregulating the expression of vascular endothelial growth factor A (VEGFA) and phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) in HUVECs. Ox-LDL exposure resulted in decreased cell viability and angiogenic capacity, coupled with increased apoptosis, inflammation, and oxidative stress in HUVECs, partially mediated by the upregulation of miR-497-5p. We confirmed VEGFA as a direct target of miR-497-5p. Interfering with VEGFA expression significantly reversed the effects mediated by miR-497-5p silencing in HUVECs exposed to ox-LDL. Conclusions: In summary, our findings demonstrate that miR-497-5p exacerbates ox-LDL-induced dysfunction in HUVECs through the activation of the p38/MAPK pathway, mediated by the targeting of VEGFA.http://www.sciencedirect.com/science/article/pii/S2405844024049181AtherosclerosisHUVECsOx-LDLmiR-497-5pVEGFAp38 |
| spellingShingle | Wei Lu Guoqing Wan He Zhu Tao Zhu Xinmei Zhang MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis Heliyon Atherosclerosis HUVECs Ox-LDL miR-497-5p VEGFA p38 |
| title | MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis |
| title_full | MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis |
| title_fullStr | MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis |
| title_full_unstemmed | MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis |
| title_short | MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis |
| title_sort | mir 497 5p regulates ox ldl induced dysfunction in vascular endothelial cells by targeting vegfa p38 mapk pathway in atherosclerosis |
| topic | Atherosclerosis HUVECs Ox-LDL miR-497-5p VEGFA p38 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024049181 |
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