دورية أكاديمية
Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis
العنوان: | Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis |
---|---|
المؤلفون: | Buono, Michele F, Benavente, Ernest Diez, Slenders, Lotte, Methorst, Daisey, Tessels, Daniëlle, Mili, Eloi, Finger, Roxy, Kapteijn, Daniek, Daniels, Mark, van den Dungen, Noortje A M, Calis, Jorg J A, Mol, Barend M, de Borst, Gert J, de Kleijn, Dominique P V, Pasterkamp, Gerard, den Ruijter, Hester M, Mokry, Michal |
المساهمون: | Experimentele Afd. Cardiologie 1, CDL Onderzoek Pasterkamp, CDL Research analisten, Cancer, Immuno/reuma onderzoek 1 (Vastert), Zorgeenheid Vaatchirurgie Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Infection & Immunity, Centraal Diagnostisch Laboratorium, Onderzoek Vrouw Hart & Vaatziekten, Child Health |
سنة النشر: | 2023 |
مصطلحات موضوعية: | disease modeling, myofibroblast, phenotypic modulation, plaque cells, smooth muscle cell, Cardiology and Cardiovascular Medicine |
الوصف: | Background Plaque myofibroblasts are critical players in the initiation and advancement of atherosclerotic disease. They are involved in the production of extracellular matrix, the formation of the fibrous cap, and the underlying lipidic core via modulation processes in response to different environmental cues. Despite clear phenotypic differences between myofibroblast cells and healthy vascular smooth muscle cells, smooth muscle cells are still widely used as a cellular model in atherosclerotic research. Methods and Results Here, we present a conditioned outgrowth method to isolate and culture myofibroblast cells from plaques. We obtained these cells from 27 donors (24 carotid and 3 femoral endarterectomies). We show that they keep their proliferative capacity for 8 passages, are transcriptionally stable, retain donor-specific gene expression programs, and express extracellular matrix proteins (FN1, COL1A1, and DCN) and smooth muscle cell markers (ACTA2, MYH11, and CNN1). Single-cell transcriptomics reveals that the cells in culture closely resemble the plaque myofibroblasts. Chromatin immunoprecipitation sequencing shows the presence of histone H3 lysine 4 dimethylation at the MYH11 promoter, pointing to their smooth muscle cell origin. Finally, we demonstrated that plaque myofibroblasts can be efficiently transduced (>97%) and are capable of taking up oxidized low-density lipoprotein and undergoing calcification. Conclusions In conclusion, we present a method to isolate and culture cells that retain plaque myofibroblast phenotypical and functional capabilities, making them a suitable in vitro model for studying selected mechanisms of atherosclerosis. |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 2047-9980 |
العلاقة: | https://dspace.library.uu.nl/handle/1874/450308Test |
الإتاحة: | https://dspace.library.uu.nl/handle/1874/450308Test |
حقوق: | info:eu-repo/semantics/OpenAccess |
رقم الانضمام: | edsbas.FD34D579 |
قاعدة البيانات: | BASE |
ResultId |
1 |
---|---|
Header |
edsbas BASE edsbas.FD34D579 975 3 Academic Journal academicJournal 975.149597167969 |
PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.FD34D579&custid=s6537998&authtype=sso |
FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://dspace.library.uu.nl/handle/1874/450308# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) [1] => Array ( [Url] => https://resolver.ebscohost.com/openurl?custid=s6537998&groupid=main&authtype=ip,guest&sid=EBSCO:edsbas&genre=article&issn=20479980&ISBN=&volume=&issue=&date=20230101&spage=&pages=&title=Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis&atitle=Human%20Plaque%20Myofibroblasts%20to%20Study%20Mechanisms%20of%20Atherosclerosis&id=DOI: [Name] => Full Text Finder (s6537998api) [Category] => fullText [Text] => Full Text Finder [Icon] => https://imageserver.ebscohost.com/branding/images/FTF.gif [MouseOverText] => Full Text Finder ) ) |
Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Buono%2C+Michele+F%22">Buono, Michele F</searchLink><br /><searchLink fieldCode="AR" term="%22Benavente%2C+Ernest+Diez%22">Benavente, Ernest Diez</searchLink><br /><searchLink fieldCode="AR" term="%22Slenders%2C+Lotte%22">Slenders, Lotte</searchLink><br /><searchLink fieldCode="AR" term="%22Methorst%2C+Daisey%22">Methorst, Daisey</searchLink><br /><searchLink fieldCode="AR" term="%22Tessels%2C+Daniëlle%22">Tessels, Daniëlle</searchLink><br /><searchLink fieldCode="AR" term="%22Mili%2C+Eloi%22">Mili, Eloi</searchLink><br /><searchLink fieldCode="AR" term="%22Finger%2C+Roxy%22">Finger, Roxy</searchLink><br /><searchLink fieldCode="AR" term="%22Kapteijn%2C+Daniek%22">Kapteijn, Daniek</searchLink><br /><searchLink fieldCode="AR" term="%22Daniels%2C+Mark%22">Daniels, Mark</searchLink><br /><searchLink fieldCode="AR" term="%22van+den+Dungen%2C+Noortje+A+M%22">van den Dungen, Noortje A M</searchLink><br /><searchLink fieldCode="AR" term="%22Calis%2C+Jorg+J+A%22">Calis, Jorg J A</searchLink><br /><searchLink fieldCode="AR" term="%22Mol%2C+Barend+M%22">Mol, Barend M</searchLink><br /><searchLink fieldCode="AR" term="%22de+Borst%2C+Gert+J%22">de Borst, Gert J</searchLink><br /><searchLink fieldCode="AR" term="%22de+Kleijn%2C+Dominique+P+V%22">de Kleijn, Dominique P V</searchLink><br /><searchLink fieldCode="AR" term="%22Pasterkamp%2C+Gerard%22">Pasterkamp, Gerard</searchLink><br /><searchLink fieldCode="AR" term="%22den+Ruijter%2C+Hester+M%22">den Ruijter, Hester M</searchLink><br /><searchLink fieldCode="AR" term="%22Mokry%2C+Michal%22">Mokry, Michal</searchLink> ) Array ( [Name] => Author [Label] => Contributors [Group] => Au [Data] => Experimentele Afd. Cardiologie 1<br />CDL Onderzoek Pasterkamp<br />CDL Research analisten<br />Cancer<br />Immuno/reuma onderzoek 1 (Vastert)<br />Zorgeenheid Vaatchirurgie Medisch<br />Circulatory Health<br />Regenerative Medicine and Stem Cells<br />Infection & Immunity<br />Centraal Diagnostisch Laboratorium<br />Onderzoek Vrouw Hart & Vaatziekten<br />Child Health ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2023 ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22disease+modeling%22">disease modeling</searchLink><br /><searchLink fieldCode="DE" term="%22myofibroblast%22">myofibroblast</searchLink><br /><searchLink fieldCode="DE" term="%22phenotypic+modulation%22">phenotypic modulation</searchLink><br /><searchLink fieldCode="DE" term="%22plaque+cells%22">plaque cells</searchLink><br /><searchLink fieldCode="DE" term="%22smooth+muscle+cell%22">smooth muscle cell</searchLink><br /><searchLink fieldCode="DE" term="%22Cardiology+and+Cardiovascular+Medicine%22">Cardiology and Cardiovascular Medicine</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => Background Plaque myofibroblasts are critical players in the initiation and advancement of atherosclerotic disease. They are involved in the production of extracellular matrix, the formation of the fibrous cap, and the underlying lipidic core via modulation processes in response to different environmental cues. Despite clear phenotypic differences between myofibroblast cells and healthy vascular smooth muscle cells, smooth muscle cells are still widely used as a cellular model in atherosclerotic research. Methods and Results Here, we present a conditioned outgrowth method to isolate and culture myofibroblast cells from plaques. We obtained these cells from 27 donors (24 carotid and 3 femoral endarterectomies). We show that they keep their proliferative capacity for 8 passages, are transcriptionally stable, retain donor-specific gene expression programs, and express extracellular matrix proteins (FN1, COL1A1, and DCN) and smooth muscle cell markers (ACTA2, MYH11, and CNN1). Single-cell transcriptomics reveals that the cells in culture closely resemble the plaque myofibroblasts. Chromatin immunoprecipitation sequencing shows the presence of histone H3 lysine 4 dimethylation at the MYH11 promoter, pointing to their smooth muscle cell origin. Finally, we demonstrated that plaque myofibroblasts can be efficiently transduced (>97%) and are capable of taking up oxidized low-density lipoprotein and undergoing calcification. Conclusions In conclusion, we present a method to isolate and culture cells that retain plaque myofibroblast phenotypical and functional capabilities, making them a suitable in vitro model for studying selected mechanisms of atherosclerosis. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article in journal/newspaper ) Array ( [Name] => Format [Label] => File Description [Group] => SrcInfo [Data] => application/pdf ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 2047-9980 ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => https://dspace.library.uu.nl/handle/1874/450308 ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => https://dspace.library.uu.nl/handle/1874/450308 ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => info:eu-repo/semantics/OpenAccess ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.FD34D579 ) |
RecordInfo |
Array
(
[BibEntity] => Array
(
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => disease modeling
[Type] => general
)
[1] => Array
(
[SubjectFull] => myofibroblast
[Type] => general
)
[2] => Array
(
[SubjectFull] => phenotypic modulation
[Type] => general
)
[3] => Array
(
[SubjectFull] => plaque cells
[Type] => general
)
[4] => Array
(
[SubjectFull] => smooth muscle cell
[Type] => general
)
[5] => Array
(
[SubjectFull] => Cardiology and Cardiovascular Medicine
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Buono, Michele F
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Benavente, Ernest Diez
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Slenders, Lotte
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Methorst, Daisey
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Tessels, Daniëlle
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Mili, Eloi
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Finger, Roxy
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kapteijn, Daniek
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Daniels, Mark
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => van den Dungen, Noortje A M
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Calis, Jorg J A
)
)
)
[11] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Mol, Barend M
)
)
)
[12] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => de Borst, Gert J
)
)
)
[13] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => de Kleijn, Dominique P V
)
)
)
[14] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Pasterkamp, Gerard
)
)
)
[15] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => den Ruijter, Hester M
)
)
)
[16] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Mokry, Michal
)
)
)
[17] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Experimentele Afd. Cardiologie 1
)
)
)
[18] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => CDL Onderzoek Pasterkamp
)
)
)
[19] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => CDL Research analisten
)
)
)
[20] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Cancer
)
)
)
[21] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Immuno/reuma onderzoek 1 (Vastert)
)
)
)
[22] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Zorgeenheid Vaatchirurgie Medisch
)
)
)
[23] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Circulatory Health
)
)
)
[24] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Regenerative Medicine and Stem Cells
)
)
)
[25] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Infection & Immunity
)
)
)
[26] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Centraal Diagnostisch Laboratorium
)
)
)
[27] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Onderzoek Vrouw Hart & Vaatziekten
)
)
)
[28] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Child Health
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2023
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 20479980
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
[2] => Array
(
[Type] => issn-locals
[Value] => edsbas.oa
)
)
)
)
)
)
)
|
IllustrationInfo |