High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects
High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/106 |
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| author | Alexy Tran-Dinh Angélique Levoye David Couret Lauriane Galle-Treger Martine Moreau Sandrine Delbosc Camille Hoteit Philippe Montravers Pierre Amarenco Thierry Huby Olivier Meilhac |
| author_facet | Alexy Tran-Dinh Angélique Levoye David Couret Lauriane Galle-Treger Martine Moreau Sandrine Delbosc Camille Hoteit Philippe Montravers Pierre Amarenco Thierry Huby Olivier Meilhac |
| author_sort | Alexy Tran-Dinh |
| collection | DOAJ |
| description | High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control and endothelial SR-BI deficient mice were intravenously injected by HDLs or saline. Infarct volume and blood-brain barrier (BBB) breakdown were assessed 24 h post tMCAO. The potential of HDLs and the role of SR-BI to maintain the BBB integrity was assessed by using a human cellular model of BBB (hCMEC/D3 cell line) subjected to oxygen-glucose deprivation (OGD). HDL therapy limited the infarct volume and the BBB leakage in control mice relative to saline injection. Interestingly, these neuroprotective effects were thwarted by the deletion of SR-BI in endothelial cells and preserved in mice deficient for SR-BI in myeloid cells. In vitro studies revealed that HDLs can preserve the integrity of the BBB in OGD conditions, and that this effect was reduced by the SR-BI inhibitor, BLT-1. The protection of BBB integrity plays a pivotal role in HDL therapy of acute ischemic stroke. Our results show that this effect is partially mediated by the HDL receptor, SR-BI expressed by endothelial cells. |
| first_indexed | 2024-03-10T13:48:12Z |
| format | Article |
| id | doaj.art-2cbc0b7927fb484a93879fd54e0ef711 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:48:12Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2cbc0b7927fb484a93879fd54e0ef7112023-11-21T02:24:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122110610.3390/ijms22010106High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective EffectsAlexy Tran-Dinh0Angélique Levoye1David Couret2Lauriane Galle-Treger3Martine Moreau4Sandrine Delbosc5Camille Hoteit6Philippe Montravers7Pierre Amarenco8Thierry Huby9Olivier Meilhac10Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1148, Bichat-Claude Bernard Hospital, Paris University, 75018 Paris, FranceParis Centre de Recherche Cardiovasculaire (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris University, 75015 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), UMR 1188, Diabète Athérothrombose Réunion Océan Indien (DéTROI), Reunion Island University, 97411 Saint-Denis de La Réunion, FranceInstitute of Cardiometabolism and Nutrition (ICAN), Institut National de la Santé et de la Recherche Médicale, UMR 1166, Sorbonne University, 75006 Paris, FranceInstitute of Cardiometabolism and Nutrition (ICAN), Institut National de la Santé et de la Recherche Médicale, UMR 1166, Sorbonne University, 75006 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), UMR 1148, Bichat-Claude Bernard Hospital, Paris University, 75018 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), UMR 1148, Bichat-Claude Bernard Hospital, Paris University, 75018 Paris, FranceDepartment of Anesthesiology and Critical Care, Bichat-Claude Bernard Hospital, AP-HP. Nord, Paris University, 75018 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), UMR 1148, Bichat-Claude Bernard Hospital, Paris University, 75018 Paris, FranceInstitute of Cardiometabolism and Nutrition (ICAN), Institut National de la Santé et de la Recherche Médicale, UMR 1166, Sorbonne University, 75006 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), UMR 1188, Diabète Athérothrombose Réunion Océan Indien (DéTROI), Reunion Island University, 97411 Saint-Denis de La Réunion, FranceHigh-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control and endothelial SR-BI deficient mice were intravenously injected by HDLs or saline. Infarct volume and blood-brain barrier (BBB) breakdown were assessed 24 h post tMCAO. The potential of HDLs and the role of SR-BI to maintain the BBB integrity was assessed by using a human cellular model of BBB (hCMEC/D3 cell line) subjected to oxygen-glucose deprivation (OGD). HDL therapy limited the infarct volume and the BBB leakage in control mice relative to saline injection. Interestingly, these neuroprotective effects were thwarted by the deletion of SR-BI in endothelial cells and preserved in mice deficient for SR-BI in myeloid cells. In vitro studies revealed that HDLs can preserve the integrity of the BBB in OGD conditions, and that this effect was reduced by the SR-BI inhibitor, BLT-1. The protection of BBB integrity plays a pivotal role in HDL therapy of acute ischemic stroke. Our results show that this effect is partially mediated by the HDL receptor, SR-BI expressed by endothelial cells.https://www.mdpi.com/1422-0067/22/1/106high-density lipoproteinSR-BIstrokeblood-brain barrier |
| spellingShingle | Alexy Tran-Dinh Angélique Levoye David Couret Lauriane Galle-Treger Martine Moreau Sandrine Delbosc Camille Hoteit Philippe Montravers Pierre Amarenco Thierry Huby Olivier Meilhac High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects International Journal of Molecular Sciences high-density lipoprotein SR-BI stroke blood-brain barrier |
| title | High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects |
| title_full | High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects |
| title_fullStr | High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects |
| title_full_unstemmed | High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects |
| title_short | High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects |
| title_sort | high density lipoprotein therapy in stroke evaluation of endothelial sr bi dependent neuroprotective effects |
| topic | high-density lipoprotein SR-BI stroke blood-brain barrier |
| url | https://www.mdpi.com/1422-0067/22/1/106 |
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