Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signaling
Abstract Background In brain, microvascular endothelial cells are exposed to various forces, including shear stress (SS). However, little is known about the effects of high shear stress (HSS) on human brain microvascular endothelial cells (HBMECs) and the underlying mechanism. The cholesterol efflux...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Neuroscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12868-022-00748-2 |
| _version_ | 1811328855977230336 |
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| author | Zhe Li Jia-Nan Li Qiang Li Chun Liu Lin-Hua Zhou Qi Zhang Yi Xu |
| author_facet | Zhe Li Jia-Nan Li Qiang Li Chun Liu Lin-Hua Zhou Qi Zhang Yi Xu |
| author_sort | Zhe Li |
| collection | DOAJ |
| description | Abstract Background In brain, microvascular endothelial cells are exposed to various forces, including shear stress (SS). However, little is known about the effects of high shear stress (HSS) on human brain microvascular endothelial cells (HBMECs) and the underlying mechanism. The cholesterol efflux regulator ATP-binding cassette subfamily A member 1 (ABCA1) has been demonstrated to exert protective effect on HBMECs. However, whether ABCA1 is involved in the mechanism underneath the effect of HSS on HBMECs remains obscure. In the present study, a series of experiments were performed to better understand the effect of HSS on cellular processes of HBMECs and the possible involvement of ABCA1 and PI3K/Akt/eNOS in the underlying mechanisms. Results HBMECs were subjected to physiological SS (PSS) or high SS (HSS). Cell migration was evaluated using Transwell assay. Apoptotic HBMECs were detected by flow cytometry or caspase3/7 activity. IL-1β, IL-6, MCP-1 and TNF-α levels were measured by ELISA. RT-qPCR and western blotting were used for mRNA and protein expression detection, respectively. ROS and NO levels were detected using specific detection kits. Compared to PSS, HBMECs exhibited decreased cell viability and migration and increased cell apoptosis, increased levels of inflammatory cytokines, and improved ROS and NO productions after HSS treatment. Moreover, HSS downregulated ABCA1 but upregulated the cholesterol efflux-related proteins MMP9, AQP4, and CYP46 and activated PI3K/Akt/eNOS pathway. Overexpression of ABCA1 in HBMECS inhibited PI3K/Akt/eNOS pathway and counteracted the deleterious effects of HSS. Contrary effects were observed by ABCA1 silencing. Inhibiting PI3K/Akt/eNOS pathway mimicked ABCA1 effects, suggesting that ABCA1 protects HBMECs from HSS via PI3K/Akt/eNOS signaling. Conclusion These results advanced our understanding on the mechanisms of HSS on HBMECs and potentiated ABCA1/PI3K/Akt/eNOS pathway as therapeutic target for cerebrovascular diseases. |
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| format | Article |
| id | doaj.art-c6df6994c52d48e591658e1cb57f7abb |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-04-13T15:33:31Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
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| series | BMC Neuroscience |
| spelling | doaj.art-c6df6994c52d48e591658e1cb57f7abb2022-12-22T02:41:20ZengBMCBMC Neuroscience1471-22022022-11-0123111310.1186/s12868-022-00748-2Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signalingZhe Li0Jia-Nan Li1Qiang Li2Chun Liu3Lin-Hua Zhou4Qi Zhang5Yi Xu6Neurovascular Center, Changhai Hospital, Naval Medical UniversityDepartment of Neurosurgery, General Hospital of Northern Theater CommandNeurovascular Center, Changhai Hospital, Naval Medical UniversityDepartment of Cerebrovascular Diseases, Blue Cross Brain Hospital Affiliated to Tongji UniversityDepartment of Cerebrovascular Diseases, Blue Cross Brain Hospital Affiliated to Tongji UniversityDepartment of Cerebrovascular Diseases, Blue Cross Brain Hospital Affiliated to Tongji UniversityNeurovascular Center, Changhai Hospital, Naval Medical UniversityAbstract Background In brain, microvascular endothelial cells are exposed to various forces, including shear stress (SS). However, little is known about the effects of high shear stress (HSS) on human brain microvascular endothelial cells (HBMECs) and the underlying mechanism. The cholesterol efflux regulator ATP-binding cassette subfamily A member 1 (ABCA1) has been demonstrated to exert protective effect on HBMECs. However, whether ABCA1 is involved in the mechanism underneath the effect of HSS on HBMECs remains obscure. In the present study, a series of experiments were performed to better understand the effect of HSS on cellular processes of HBMECs and the possible involvement of ABCA1 and PI3K/Akt/eNOS in the underlying mechanisms. Results HBMECs were subjected to physiological SS (PSS) or high SS (HSS). Cell migration was evaluated using Transwell assay. Apoptotic HBMECs were detected by flow cytometry or caspase3/7 activity. IL-1β, IL-6, MCP-1 and TNF-α levels were measured by ELISA. RT-qPCR and western blotting were used for mRNA and protein expression detection, respectively. ROS and NO levels were detected using specific detection kits. Compared to PSS, HBMECs exhibited decreased cell viability and migration and increased cell apoptosis, increased levels of inflammatory cytokines, and improved ROS and NO productions after HSS treatment. Moreover, HSS downregulated ABCA1 but upregulated the cholesterol efflux-related proteins MMP9, AQP4, and CYP46 and activated PI3K/Akt/eNOS pathway. Overexpression of ABCA1 in HBMECS inhibited PI3K/Akt/eNOS pathway and counteracted the deleterious effects of HSS. Contrary effects were observed by ABCA1 silencing. Inhibiting PI3K/Akt/eNOS pathway mimicked ABCA1 effects, suggesting that ABCA1 protects HBMECs from HSS via PI3K/Akt/eNOS signaling. Conclusion These results advanced our understanding on the mechanisms of HSS on HBMECs and potentiated ABCA1/PI3K/Akt/eNOS pathway as therapeutic target for cerebrovascular diseases.https://doi.org/10.1186/s12868-022-00748-2ABCA1AtherosclerosisCholesterol effluxHigh shear stressHuman brain microvascular endothelial cellsPI3K/Akt/eNOS pathway |
| spellingShingle | Zhe Li Jia-Nan Li Qiang Li Chun Liu Lin-Hua Zhou Qi Zhang Yi Xu Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signaling BMC Neuroscience ABCA1 Atherosclerosis Cholesterol efflux High shear stress Human brain microvascular endothelial cells PI3K/Akt/eNOS pathway |
| title | Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signaling |
| title_full | Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signaling |
| title_fullStr | Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signaling |
| title_full_unstemmed | Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signaling |
| title_short | Cholesterol efflux regulator ABCA1 exerts protective role against high shear stress-induced injury of HBMECs via regulating PI3K/Akt/eNOS signaling |
| title_sort | cholesterol efflux regulator abca1 exerts protective role against high shear stress induced injury of hbmecs via regulating pi3k akt enos signaling |
| topic | ABCA1 Atherosclerosis Cholesterol efflux High shear stress Human brain microvascular endothelial cells PI3K/Akt/eNOS pathway |
| url | https://doi.org/10.1186/s12868-022-00748-2 |
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