Genetic ablation of myeloid integrin α9 attenuates early atherosclerosis
Integrin α9β1 is known to stabilize leukocyte adhesion to the activated endothelium. We determined the role of myeloid cell α9β1 in early atherosclerosis in two models: α9Mye-KOApoe-/- or the Ldlr-/- mice transplanted with bone marrow (BM) from α9Mye-KO mice fed a high-fat "Western" diet f...
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| Veröffentlicht in: | Journal of leukocyte biology 2024-11, Vol.116 (5), p.1208-1214 |
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| creator | Barbhuyan, Tarun Patel, Rakesh B Budnik, Ivan Chauhan, Anil K |
| description | Integrin α9β1 is known to stabilize leukocyte adhesion to the activated endothelium. We determined the role of myeloid cell α9β1 in early atherosclerosis in two models: α9Mye-KOApoe-/- or the Ldlr-/- mice transplanted with bone marrow (BM) from α9Mye-KO mice fed a high-fat "Western" diet for 4 wk. α9Mye-KOApoe-/- mice exhibited reduced early lesions in the aortae and aortic sinuses (P < 0.05 vs α9WT Apoe-/- mice). Similar results were obtained in α9Mye-KO BM→Ldlr-/- mice (P < 0.05 vs α9WT BM→Ldlr-/- mice). Reduced early atherosclerosis in α9Mye-KOApoe-/- mice was associated with decreased neutrophil and neutrophil extracellular traps (NETs) content in the aortic lesions (P < 0.05 vs α9WTApoe-/-). Vascular cell adhesion molecule-1-stimulated neutrophils from α9Mye-KO mice exhibited reduced adhesion, transmigration, and NETs formation (NETosis) (P < 0.05 vs α9WT neutrophils). Reduced NETosis was associated with decreased extracellular signal-regulated kinase phosphorylation, peptidyl arginine deiminase 4, and citrullinated histone H3 expression. In summary, genetic ablation of myeloid cell-specific α9 reduces early atherosclerosis, most likely by reducing neutrophil adhesion, transmigration, and NETosis. |
| doi_str_mv | 10.1093/jleuko/qiae161 |
| format | Article |
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We determined the role of myeloid cell α9β1 in early atherosclerosis in two models: α9Mye-KOApoe-/- or the Ldlr-/- mice transplanted with bone marrow (BM) from α9Mye-KO mice fed a high-fat "Western" diet for 4 wk. α9Mye-KOApoe-/- mice exhibited reduced early lesions in the aortae and aortic sinuses (P < 0.05 vs α9WT Apoe-/- mice). Similar results were obtained in α9Mye-KO BM→Ldlr-/- mice (P < 0.05 vs α9WT BM→Ldlr-/- mice). Reduced early atherosclerosis in α9Mye-KOApoe-/- mice was associated with decreased neutrophil and neutrophil extracellular traps (NETs) content in the aortic lesions (P < 0.05 vs α9WTApoe-/-). Vascular cell adhesion molecule-1-stimulated neutrophils from α9Mye-KO mice exhibited reduced adhesion, transmigration, and NETs formation (NETosis) (P < 0.05 vs α9WT neutrophils). Reduced NETosis was associated with decreased extracellular signal-regulated kinase phosphorylation, peptidyl arginine deiminase 4, and citrullinated histone H3 expression. In summary, genetic ablation of myeloid cell-specific α9 reduces early atherosclerosis, most likely by reducing neutrophil adhesion, transmigration, and NETosis.</description><identifier>ISSN: 1938-3673</identifier><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1093/jleuko/qiae161</identifier><identifier>PMID: 39036986</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Aorta - metabolism ; Aorta - pathology ; Atherosclerosis - genetics ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Brief Report ; Cell Adhesion ; Extracellular Traps - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Cells - metabolism ; Myeloid Cells - pathology ; Neutrophils - metabolism ; Receptors, LDL - genetics ; Vascular Cell Adhesion Molecule-1 - genetics ; Vascular Cell Adhesion Molecule-1 - metabolism</subject><ispartof>Journal of leukocyte biology, 2024-11, Vol.116 (5), p.1208-1214</ispartof><rights>The Author(s) 2024. 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We determined the role of myeloid cell α9β1 in early atherosclerosis in two models: α9Mye-KOApoe-/- or the Ldlr-/- mice transplanted with bone marrow (BM) from α9Mye-KO mice fed a high-fat "Western" diet for 4 wk. α9Mye-KOApoe-/- mice exhibited reduced early lesions in the aortae and aortic sinuses (P < 0.05 vs α9WT Apoe-/- mice). Similar results were obtained in α9Mye-KO BM→Ldlr-/- mice (P < 0.05 vs α9WT BM→Ldlr-/- mice). Reduced early atherosclerosis in α9Mye-KOApoe-/- mice was associated with decreased neutrophil and neutrophil extracellular traps (NETs) content in the aortic lesions (P < 0.05 vs α9WTApoe-/-). Vascular cell adhesion molecule-1-stimulated neutrophils from α9Mye-KO mice exhibited reduced adhesion, transmigration, and NETs formation (NETosis) (P < 0.05 vs α9WT neutrophils). Reduced NETosis was associated with decreased extracellular signal-regulated kinase phosphorylation, peptidyl arginine deiminase 4, and citrullinated histone H3 expression. In summary, genetic ablation of myeloid cell-specific α9 reduces early atherosclerosis, most likely by reducing neutrophil adhesion, transmigration, and NETosis.</description><subject>Animals</subject><subject>Aorta - metabolism</subject><subject>Aorta - pathology</subject><subject>Atherosclerosis - genetics</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - pathology</subject><subject>Brief Report</subject><subject>Cell Adhesion</subject><subject>Extracellular Traps - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myeloid Cells - metabolism</subject><subject>Myeloid Cells - pathology</subject><subject>Neutrophils - metabolism</subject><subject>Receptors, LDL - genetics</subject><subject>Vascular Cell Adhesion Molecule-1 - genetics</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><issn>1938-3673</issn><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1PAjEQbYxGEL16NHv0AkzptmxPxhhFEhIvem663Vkoli1suyb8LP-Iv8klIMHLzGTmzZuPR8gthQEFyYZLh82nH26sRiroGelSybI-E2N2fhJ3yFUISwBgIwGXpMMkMCEz0SXTCVYYrUl07nS0vkp8may26LwtEltFnNe2Sn6-ZaJjxKrREUOCunbbNrHA2gfjdtaGa3JRahfw5uB75OPl-f3ptT97m0yfHmd9M2Ii9scFpIVIxznlkpsUOeiU5hwETXkpyxSYydq9UygywYxEBM4F6NyARJ2NStYjD3vedZOvsDBYxVo7ta7tStdb5bVV_yuVXai5_1KUckYzEC3D_YGh9psGQ1QrGww6pyv0TVAMMjaiUgjeQgd7qGlvDDWWxzkU1E4AtRdAHQRoG-5OtzvC_z7OfgEg14X2</recordid><startdate>20241104</startdate><enddate>20241104</enddate><creator>Barbhuyan, Tarun</creator><creator>Patel, Rakesh B</creator><creator>Budnik, Ivan</creator><creator>Chauhan, Anil K</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8554-0898</orcidid></search><sort><creationdate>20241104</creationdate><title>Genetic ablation of myeloid integrin α9 attenuates early atherosclerosis</title><author>Barbhuyan, Tarun ; Patel, Rakesh B ; Budnik, Ivan ; Chauhan, Anil K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c236t-7d04d647b1595c4e50a41b506145f9f403c819340d863c9ee05560abc09ea82f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Aorta - metabolism</topic><topic>Aorta - pathology</topic><topic>Atherosclerosis - genetics</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - pathology</topic><topic>Brief Report</topic><topic>Cell Adhesion</topic><topic>Extracellular Traps - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myeloid Cells - metabolism</topic><topic>Myeloid Cells - pathology</topic><topic>Neutrophils - metabolism</topic><topic>Receptors, LDL - genetics</topic><topic>Vascular Cell Adhesion Molecule-1 - genetics</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barbhuyan, Tarun</creatorcontrib><creatorcontrib>Patel, Rakesh B</creatorcontrib><creatorcontrib>Budnik, Ivan</creatorcontrib><creatorcontrib>Chauhan, Anil K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barbhuyan, Tarun</au><au>Patel, Rakesh B</au><au>Budnik, Ivan</au><au>Chauhan, Anil K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic ablation of myeloid integrin α9 attenuates early atherosclerosis</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2024-11-04</date><risdate>2024</risdate><volume>116</volume><issue>5</issue><spage>1208</spage><epage>1214</epage><pages>1208-1214</pages><issn>1938-3673</issn><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>Integrin α9β1 is known to stabilize leukocyte adhesion to the activated endothelium. We determined the role of myeloid cell α9β1 in early atherosclerosis in two models: α9Mye-KOApoe-/- or the Ldlr-/- mice transplanted with bone marrow (BM) from α9Mye-KO mice fed a high-fat "Western" diet for 4 wk. α9Mye-KOApoe-/- mice exhibited reduced early lesions in the aortae and aortic sinuses (P < 0.05 vs α9WT Apoe-/- mice). Similar results were obtained in α9Mye-KO BM→Ldlr-/- mice (P < 0.05 vs α9WT BM→Ldlr-/- mice). Reduced early atherosclerosis in α9Mye-KOApoe-/- mice was associated with decreased neutrophil and neutrophil extracellular traps (NETs) content in the aortic lesions (P < 0.05 vs α9WTApoe-/-). Vascular cell adhesion molecule-1-stimulated neutrophils from α9Mye-KO mice exhibited reduced adhesion, transmigration, and NETs formation (NETosis) (P < 0.05 vs α9WT neutrophils). Reduced NETosis was associated with decreased extracellular signal-regulated kinase phosphorylation, peptidyl arginine deiminase 4, and citrullinated histone H3 expression. In summary, genetic ablation of myeloid cell-specific α9 reduces early atherosclerosis, most likely by reducing neutrophil adhesion, transmigration, and NETosis.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>39036986</pmid><doi>10.1093/jleuko/qiae161</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-8554-0898</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Animals Aorta - metabolism Aorta - pathology Atherosclerosis - genetics Atherosclerosis - metabolism Atherosclerosis - pathology Brief Report Cell Adhesion Extracellular Traps - metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Myeloid Cells - metabolism Myeloid Cells - pathology Neutrophils - metabolism Receptors, LDL - genetics Vascular Cell Adhesion Molecule-1 - genetics Vascular Cell Adhesion Molecule-1 - metabolism |
| title | Genetic ablation of myeloid integrin α9 attenuates early atherosclerosis |
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