Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1
Atherosclerosis results from the deposition and oxidation of LDL and immune cell infiltration in the sub-arterial space leading to arterial occlusion. Studies have shown that transcytosis transports circulating LDL across endothelial cells lining blood vessels. LDL transcytosis is initiated by bindi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752400035X |
| _version_ | 1797219345790664704 |
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| author | Karen Y.Y. Fung Tse Wing Winnie Ho Zizhen Xu Dante Neculai Catherine A.A. Beauchemin Warren L. Lee Gregory D. Fairn |
| author_facet | Karen Y.Y. Fung Tse Wing Winnie Ho Zizhen Xu Dante Neculai Catherine A.A. Beauchemin Warren L. Lee Gregory D. Fairn |
| author_sort | Karen Y.Y. Fung |
| collection | DOAJ |
| description | Atherosclerosis results from the deposition and oxidation of LDL and immune cell infiltration in the sub-arterial space leading to arterial occlusion. Studies have shown that transcytosis transports circulating LDL across endothelial cells lining blood vessels. LDL transcytosis is initiated by binding to either scavenger receptor B1 (SR-B1) or activin A receptor-like kinase 1 on the apical side of endothelial cells leading to its transit and release on the basolateral side. HDL is thought to partly protect individuals from atherosclerosis due to its ability to remove excess cholesterol and act as an antioxidant. Apolipoprotein A1 (APOA1), an HDL constituent, can bind to SR-B1, raising the possibility that APOA1/HDL can compete with LDL for SR-B1 binding, thereby limiting LDL deposition in the sub-arterial space. To examine this possibility, we used in vitro approaches to quantify the internalization and transcytosis of fluorescent LDL in coronary endothelial cells. Using microscale thermophoresis and affinity capture, we find that SR-B1 and APOA1 interact and that binding is enhanced when using the cardioprotective variant of APOA1 termed Milano (APOA1-Milano). In male mice, transiently increasing the levels of HDL reduced the acute deposition of fluorescently labeled LDL in the atheroprone inner curvature of the aorta. Reduced LDL deposition was also observed when increasing circulating wild-type APOA1 or the APOA1-Milano variant, with a more robust inhibition from the APOA1-Milano. The results suggest that HDL may limit SR-B1-mediated LDL transcytosis and deposition, adding to the mechanisms by which it can act as an atheroprotective particle. |
| first_indexed | 2024-04-24T12:32:11Z |
| format | Article |
| id | doaj.art-b4bb9fad0525489c85d0f1702220cdfe |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-24T12:32:11Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-b4bb9fad0525489c85d0f1702220cdfe2024-04-08T04:08:09ZengElsevierJournal of Lipid Research0022-22752024-04-01654100530Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1Karen Y.Y. Fung0Tse Wing Winnie Ho1Zizhen Xu2Dante Neculai3Catherine A.A. Beauchemin4Warren L. Lee5Gregory D. Fairn6Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada; Keenan Research Centre, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, CanadaKeenan Research Centre, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, CanadaDepartment of Cell Biology, and Department of Pathology Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Department of Pathology Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Physics, Toronto Metropolitan University, Toronto, Ontario, Canada; Interdisciplinary Theoretical and Mathematical Sciences (iTHEMS) program, RIKEN, Wako, Saitama, JapanDepartment of Biochemistry, University of Toronto, Toronto, Ontario, Canada; Keenan Research Centre, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; For correspondence: Warren L. Lee; Gregory D. FairnDepartment of Biochemistry, University of Toronto, Toronto, Ontario, Canada; Keenan Research Centre, St. Michael’s Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada; For correspondence: Warren L. Lee; Gregory D. FairnAtherosclerosis results from the deposition and oxidation of LDL and immune cell infiltration in the sub-arterial space leading to arterial occlusion. Studies have shown that transcytosis transports circulating LDL across endothelial cells lining blood vessels. LDL transcytosis is initiated by binding to either scavenger receptor B1 (SR-B1) or activin A receptor-like kinase 1 on the apical side of endothelial cells leading to its transit and release on the basolateral side. HDL is thought to partly protect individuals from atherosclerosis due to its ability to remove excess cholesterol and act as an antioxidant. Apolipoprotein A1 (APOA1), an HDL constituent, can bind to SR-B1, raising the possibility that APOA1/HDL can compete with LDL for SR-B1 binding, thereby limiting LDL deposition in the sub-arterial space. To examine this possibility, we used in vitro approaches to quantify the internalization and transcytosis of fluorescent LDL in coronary endothelial cells. Using microscale thermophoresis and affinity capture, we find that SR-B1 and APOA1 interact and that binding is enhanced when using the cardioprotective variant of APOA1 termed Milano (APOA1-Milano). In male mice, transiently increasing the levels of HDL reduced the acute deposition of fluorescently labeled LDL in the atheroprone inner curvature of the aorta. Reduced LDL deposition was also observed when increasing circulating wild-type APOA1 or the APOA1-Milano variant, with a more robust inhibition from the APOA1-Milano. The results suggest that HDL may limit SR-B1-mediated LDL transcytosis and deposition, adding to the mechanisms by which it can act as an atheroprotective particle.http://www.sciencedirect.com/science/article/pii/S002222752400035Xapolipoprotein A1HDLLDLtranscytosisatherosclerosis |
| spellingShingle | Karen Y.Y. Fung Tse Wing Winnie Ho Zizhen Xu Dante Neculai Catherine A.A. Beauchemin Warren L. Lee Gregory D. Fairn Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1 Journal of Lipid Research apolipoprotein A1 HDL LDL transcytosis atherosclerosis |
| title | Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1 |
| title_full | Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1 |
| title_fullStr | Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1 |
| title_full_unstemmed | Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1 |
| title_short | Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1 |
| title_sort | apolipoprotein a1 and high density lipoprotein limit low density lipoprotein transcytosis by binding sr b1 |
| topic | apolipoprotein A1 HDL LDL transcytosis atherosclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S002222752400035X |
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