Proteomic Profiling of Exosomes From Hemorrhagic Moyamoya Disease and Dysfunction of Mitochondria in Endothelial Cells
Moyamoya disease (MMD) is a rare steno-occlusive and slowly progressing cerebrovascular disorder. The detailed mechanism of the underlying pathogenesis is still blurry. Tandem Mass Tag-labeled quantitative proteomics was performed on serum-derived exosomes (SDEs) extracted from adult patients diagno...
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Veröffentlicht in: | Stroke (1970) 2021-10, Vol.52 (10), p.3351-3361 |
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description | Moyamoya disease (MMD) is a rare steno-occlusive and slowly progressing cerebrovascular disorder. The detailed mechanism of the underlying pathogenesis is still blurry.
Tandem Mass Tag-labeled quantitative proteomics was performed on serum-derived exosomes (SDEs) extracted from adult patients diagnosed with pure ischemic MMD or hemorrhagic MMD and healthy controls. Then mouse brain vascular endothelial cell (EC), human umbilical vein EC, neuroblastoma cell, and human hepatocyte cell were treated with exosomes, and changes of the protein expression in mouse brain vascular EC cells were identified.
Proteomics analysis results showed that 859 shared proteins were detected in SDEs from ischemic and hemorrhagic MMD patients with 231 differently expressed compared with healthy controls. Bioinformatic analysis revealed dysregulated cell growth and maintenance and indicated disturbed actin dynamics in MMD, with CFL1 (Cofilin-1) and ACTR2/3 (actin-related protein 2/3; also known as ARP2/3) downregulated in ischemic and hemorrhagic patients’ SDEs. We also found immunity dysfunction in hemorrhagic MMD. Following treatment with MMD SDEs, mouse brain vascular EC cells showed significantly higher levels of proliferation and more ethynyl-2-deoxyuridine-positive cells compared with the healthy control group, while there were no obvious changes in the human umbilical vein EC and human hepatocyte cell. Interestingly, we also found that SDEs from ischemic MMD promoted neuroblastoma cell proliferation. Proteomic analysis of mouse brain vascular EC cells suggested that SDEs from hemorrhagic MMD patients induced dysfunction of the mitochondria in cerebrovascular ECs.
This study highlighted potential molecular mechanisms underlying the pathogenesis of MMD patients, thereby providing new therapeutic strategies for MMD. |
doi_str_mv | 10.1161/STROKEAHA.120.032297 |
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Tandem Mass Tag-labeled quantitative proteomics was performed on serum-derived exosomes (SDEs) extracted from adult patients diagnosed with pure ischemic MMD or hemorrhagic MMD and healthy controls. Then mouse brain vascular endothelial cell (EC), human umbilical vein EC, neuroblastoma cell, and human hepatocyte cell were treated with exosomes, and changes of the protein expression in mouse brain vascular EC cells were identified.
Proteomics analysis results showed that 859 shared proteins were detected in SDEs from ischemic and hemorrhagic MMD patients with 231 differently expressed compared with healthy controls. Bioinformatic analysis revealed dysregulated cell growth and maintenance and indicated disturbed actin dynamics in MMD, with CFL1 (Cofilin-1) and ACTR2/3 (actin-related protein 2/3; also known as ARP2/3) downregulated in ischemic and hemorrhagic patients’ SDEs. We also found immunity dysfunction in hemorrhagic MMD. Following treatment with MMD SDEs, mouse brain vascular EC cells showed significantly higher levels of proliferation and more ethynyl-2-deoxyuridine-positive cells compared with the healthy control group, while there were no obvious changes in the human umbilical vein EC and human hepatocyte cell. Interestingly, we also found that SDEs from ischemic MMD promoted neuroblastoma cell proliferation. Proteomic analysis of mouse brain vascular EC cells suggested that SDEs from hemorrhagic MMD patients induced dysfunction of the mitochondria in cerebrovascular ECs.
This study highlighted potential molecular mechanisms underlying the pathogenesis of MMD patients, thereby providing new therapeutic strategies for MMD.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/STROKEAHA.120.032297</identifier><identifier>PMID: 34334053</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins</publisher><subject>Adult ; Animals ; Brain Ischemia - etiology ; Brain Ischemia - genetics ; Cell Proliferation ; Computational Biology ; Endothelial Cells ; Exosomes - genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation - genetics ; Hepatocytes - pathology ; Human Umbilical Vein Endothelial Cells ; Humans ; Intracranial Hemorrhages - etiology ; Intracranial Hemorrhages - genetics ; Male ; Mice ; Middle Aged ; Mitochondrial Diseases - genetics ; Moyamoya Disease - complications ; Moyamoya Disease - genetics ; Proteomics ; Young Adult</subject><ispartof>Stroke (1970), 2021-10, Vol.52 (10), p.3351-3361</ispartof><rights>Lippincott Williams & Wilkins</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4646-5ef88a09d2cad5ea0083ec1fa74137f6847878676940f43b86c0fed8226de0323</citedby><cites>FETCH-LOGICAL-c4646-5ef88a09d2cad5ea0083ec1fa74137f6847878676940f43b86c0fed8226de0323</cites><orcidid>0000-0001-7210-056X ; 0000-0002-9907-512X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34334053$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xia</creatorcontrib><creatorcontrib>Han, Cong</creatorcontrib><creatorcontrib>Jia, Yangjie</creatorcontrib><creatorcontrib>Wang, Jiayu</creatorcontrib><creatorcontrib>Ge, Wei</creatorcontrib><creatorcontrib>Duan, Lian</creatorcontrib><title>Proteomic Profiling of Exosomes From Hemorrhagic Moyamoya Disease and Dysfunction of Mitochondria in Endothelial Cells</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>Moyamoya disease (MMD) is a rare steno-occlusive and slowly progressing cerebrovascular disorder. The detailed mechanism of the underlying pathogenesis is still blurry.
Tandem Mass Tag-labeled quantitative proteomics was performed on serum-derived exosomes (SDEs) extracted from adult patients diagnosed with pure ischemic MMD or hemorrhagic MMD and healthy controls. Then mouse brain vascular endothelial cell (EC), human umbilical vein EC, neuroblastoma cell, and human hepatocyte cell were treated with exosomes, and changes of the protein expression in mouse brain vascular EC cells were identified.
Proteomics analysis results showed that 859 shared proteins were detected in SDEs from ischemic and hemorrhagic MMD patients with 231 differently expressed compared with healthy controls. Bioinformatic analysis revealed dysregulated cell growth and maintenance and indicated disturbed actin dynamics in MMD, with CFL1 (Cofilin-1) and ACTR2/3 (actin-related protein 2/3; also known as ARP2/3) downregulated in ischemic and hemorrhagic patients’ SDEs. We also found immunity dysfunction in hemorrhagic MMD. Following treatment with MMD SDEs, mouse brain vascular EC cells showed significantly higher levels of proliferation and more ethynyl-2-deoxyuridine-positive cells compared with the healthy control group, while there were no obvious changes in the human umbilical vein EC and human hepatocyte cell. Interestingly, we also found that SDEs from ischemic MMD promoted neuroblastoma cell proliferation. Proteomic analysis of mouse brain vascular EC cells suggested that SDEs from hemorrhagic MMD patients induced dysfunction of the mitochondria in cerebrovascular ECs.
This study highlighted potential molecular mechanisms underlying the pathogenesis of MMD patients, thereby providing new therapeutic strategies for MMD.</description><subject>Adult</subject><subject>Animals</subject><subject>Brain Ischemia - etiology</subject><subject>Brain Ischemia - genetics</subject><subject>Cell Proliferation</subject><subject>Computational Biology</subject><subject>Endothelial Cells</subject><subject>Exosomes - genetics</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - genetics</subject><subject>Hepatocytes - pathology</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Intracranial Hemorrhages - etiology</subject><subject>Intracranial Hemorrhages - genetics</subject><subject>Male</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Mitochondrial Diseases - genetics</subject><subject>Moyamoya Disease - complications</subject><subject>Moyamoya Disease - genetics</subject><subject>Proteomics</subject><subject>Young Adult</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkU1v1DAQhi1ERZfCP0DIRy5Zxh9xnONqu2Wrtipqy9lyk3FjSOJiJ5T993i1pT2MZkZ635nRM4R8YrBkTLGvt3c31xeb1Xa1ZByWIDivqzdkwUouC6m4fksWAKIuuKzrY_I-pZ8AwIUu35FjIYWQUIoF-fM9hgnD4BuaK-d7Pz7Q4Ojmb0hhwETPYhjoFocQY2cfsuwq7OyQg576hDYhtWNLT3fJzWMz-TDu3Vd-Ck0XxjZ6S_1IN2Mbpg57b3u6xr5PH8iRs33Cj8_5hPw429ytt8Xl9bfz9eqyaKSSqijRaW2hbnlj2xItgBbYMGcryUTllJaVrrSqVC3BSXGvVQMOW825ajEjESfky2HuYwy_Z0yTGXxq8gV2xDAnw8uyKiUwXmepPEibGFKK6Mxj9IONO8PA7ImbF-ImEzcH4tn2-XnDfD9g-2L6j_h17lPoJ4zpVz8_YTQd2n7qTP4JVKqCggNnbN8VOYQS_wDC_I1_</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Wang, Xia</creator><creator>Han, Cong</creator><creator>Jia, Yangjie</creator><creator>Wang, Jiayu</creator><creator>Ge, Wei</creator><creator>Duan, Lian</creator><general>Lippincott Williams & Wilkins</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><orcidid>https://orcid.org/0000-0001-7210-056X</orcidid><orcidid>https://orcid.org/0000-0002-9907-512X</orcidid></search><sort><creationdate>20211001</creationdate><title>Proteomic Profiling of Exosomes From Hemorrhagic Moyamoya Disease and Dysfunction of Mitochondria in Endothelial Cells</title><author>Wang, Xia ; Han, Cong ; Jia, Yangjie ; Wang, Jiayu ; Ge, Wei ; Duan, Lian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4646-5ef88a09d2cad5ea0083ec1fa74137f6847878676940f43b86c0fed8226de0323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Brain Ischemia - etiology</topic><topic>Brain Ischemia - genetics</topic><topic>Cell Proliferation</topic><topic>Computational Biology</topic><topic>Endothelial Cells</topic><topic>Exosomes - genetics</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation - genetics</topic><topic>Hepatocytes - pathology</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Intracranial Hemorrhages - etiology</topic><topic>Intracranial Hemorrhages - genetics</topic><topic>Male</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Mitochondrial Diseases - genetics</topic><topic>Moyamoya Disease - complications</topic><topic>Moyamoya Disease - genetics</topic><topic>Proteomics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xia</creatorcontrib><creatorcontrib>Han, Cong</creatorcontrib><creatorcontrib>Jia, Yangjie</creatorcontrib><creatorcontrib>Wang, Jiayu</creatorcontrib><creatorcontrib>Ge, Wei</creatorcontrib><creatorcontrib>Duan, Lian</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><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xia</au><au>Han, Cong</au><au>Jia, Yangjie</au><au>Wang, Jiayu</au><au>Ge, Wei</au><au>Duan, Lian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteomic Profiling of Exosomes From Hemorrhagic Moyamoya Disease and Dysfunction of Mitochondria in Endothelial Cells</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>52</volume><issue>10</issue><spage>3351</spage><epage>3361</epage><pages>3351-3361</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><abstract>Moyamoya disease (MMD) is a rare steno-occlusive and slowly progressing cerebrovascular disorder. The detailed mechanism of the underlying pathogenesis is still blurry.
Tandem Mass Tag-labeled quantitative proteomics was performed on serum-derived exosomes (SDEs) extracted from adult patients diagnosed with pure ischemic MMD or hemorrhagic MMD and healthy controls. Then mouse brain vascular endothelial cell (EC), human umbilical vein EC, neuroblastoma cell, and human hepatocyte cell were treated with exosomes, and changes of the protein expression in mouse brain vascular EC cells were identified.
Proteomics analysis results showed that 859 shared proteins were detected in SDEs from ischemic and hemorrhagic MMD patients with 231 differently expressed compared with healthy controls. Bioinformatic analysis revealed dysregulated cell growth and maintenance and indicated disturbed actin dynamics in MMD, with CFL1 (Cofilin-1) and ACTR2/3 (actin-related protein 2/3; also known as ARP2/3) downregulated in ischemic and hemorrhagic patients’ SDEs. We also found immunity dysfunction in hemorrhagic MMD. Following treatment with MMD SDEs, mouse brain vascular EC cells showed significantly higher levels of proliferation and more ethynyl-2-deoxyuridine-positive cells compared with the healthy control group, while there were no obvious changes in the human umbilical vein EC and human hepatocyte cell. Interestingly, we also found that SDEs from ischemic MMD promoted neuroblastoma cell proliferation. Proteomic analysis of mouse brain vascular EC cells suggested that SDEs from hemorrhagic MMD patients induced dysfunction of the mitochondria in cerebrovascular ECs.
This study highlighted potential molecular mechanisms underlying the pathogenesis of MMD patients, thereby providing new therapeutic strategies for MMD.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins</pub><pmid>34334053</pmid><doi>10.1161/STROKEAHA.120.032297</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7210-056X</orcidid><orcidid>https://orcid.org/0000-0002-9907-512X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adult Animals Brain Ischemia - etiology Brain Ischemia - genetics Cell Proliferation Computational Biology Endothelial Cells Exosomes - genetics Female Gene Expression Profiling Gene Expression Regulation - genetics Hepatocytes - pathology Human Umbilical Vein Endothelial Cells Humans Intracranial Hemorrhages - etiology Intracranial Hemorrhages - genetics Male Mice Middle Aged Mitochondrial Diseases - genetics Moyamoya Disease - complications Moyamoya Disease - genetics Proteomics Young Adult |
title | Proteomic Profiling of Exosomes From Hemorrhagic Moyamoya Disease and Dysfunction of Mitochondria in Endothelial Cells |
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