Atherosclerotic patients have lower levels of BLTR1 expressing microvesicles compared to healthy individuals

Background: Monocytes/macrophages play a crucial role in the development, progression, and complication of atherosclerosis. In particular, foam cell formation driven by CD36 mediated internalisation of oxLDL leads to activation of monocytes and subsequent release of monocytederived microvesicles (MM...

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Veröffentlicht in:Journal of extracellular vesicles 2018-01, Vol.7, p.71-71
Hauptverfasser: Sanden, Mathilde, Botha, Jaco, Nielsen, Michael René Skjelbo, Nielsen, Morten Hjuler, Schmidt, Erik Berg, Handberg, Aase
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container_end_page 71
container_issue
container_start_page 71
container_title Journal of extracellular vesicles
container_volume 7
creator Sanden, Mathilde
Botha, Jaco
Nielsen, Michael René Skjelbo
Nielsen, Morten Hjuler
Schmidt, Erik Berg
Handberg, Aase
description Background: Monocytes/macrophages play a crucial role in the development, progression, and complication of atherosclerosis. In particular, foam cell formation driven by CD36 mediated internalisation of oxLDL leads to activation of monocytes and subsequent release of monocytederived microvesicles (MMVs). Further, pro-inflammatory leukotriene B4 derived from arachidonic acid (AA) promotes atherosclerosis through the high-affinity receptor BLTR1. Thus, we aimed to investigate the correlation between different MMV phenotypes on the one hand, and AA and eicosapentaenoic acid (EPA) contents in different compartments including atherosclerotic plaques, plasma and granulocytes on the other. This might elucidate the potential of CD36 and BLTR1 bearing MMV phenotypes as novel biomarkers in predicting atherosclerosis. Methods: Plasma samples from 48 subjects with femoral atherosclerosis and 24 healthy controls were analysed on an Apogee A60 MicroPLUS flow cytometer. Platelet-poor plasma was labelled with lactadherin-FITC, anti-CD14-APC, anti-CD36-PE and anti-BLTR1-AF700. MVs were defined as phosphatidylserine-exposing (PS+) events
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In particular, foam cell formation driven by CD36 mediated internalisation of oxLDL leads to activation of monocytes and subsequent release of monocytederived microvesicles (MMVs). Further, pro-inflammatory leukotriene B4 derived from arachidonic acid (AA) promotes atherosclerosis through the high-affinity receptor BLTR1. Thus, we aimed to investigate the correlation between different MMV phenotypes on the one hand, and AA and eicosapentaenoic acid (EPA) contents in different compartments including atherosclerotic plaques, plasma and granulocytes on the other. This might elucidate the potential of CD36 and BLTR1 bearing MMV phenotypes as novel biomarkers in predicting atherosclerosis. Methods: Plasma samples from 48 subjects with femoral atherosclerosis and 24 healthy controls were analysed on an Apogee A60 MicroPLUS flow cytometer. Platelet-poor plasma was labelled with lactadherin-FITC, anti-CD14-APC, anti-CD36-PE and anti-BLTR1-AF700. MVs were defined as phosphatidylserine-exposing (PS+) events &lt;1000 nm in size. EPA and AA content in granulocytes, plasma phospholipids and atherosclerotic plaques were analysed using gas chromatography. Results: Patients with atherosclerosis had lower levels of BLTR1+ MVs (p = 0.007), CD14+BLTR1+ MVs (p = 0.007) and CD14+BLTR1+CD36+ MVs (p = 0.001) compared to healthy controls. Further, CD14+ MVs and CD14+CD36+ MVs correlated negatively with AA in granulocytes (r = -0.302, p = 0.039 and r = -0.322, p = 0.028, respectively). CD14 +CD36+ MVs correlated negatively with AA in plasma phospholipids (r = -0.315, p = 0.029). Lastly, CD14+ MVs and CD14+BLTR1+ MVs tended to correlate inversely with AA in plasma phospholipids and AA in atherosclerotic plaques, respectively (r = -0.284, p = 0.050 and r = - 0.291, p = 0.058). Summary/Conclusion: We demonstrated that atherosclerotic patients had lower levels of BLTR1+ MV phenotypes compared to healthy individuals. This is possibly caused by higher levels of LTB4 and inflammatory cytokines in patients which leads to receptor downregulation. Further investigations into the origin and phenotype may support the potential of circulating MVs in early diagnosis of atherosclerosis.</description><identifier>EISSN: 2001-3078</identifier><language>eng</language><publisher>Abingdon: John Wiley &amp; Sons, Inc</publisher><subject>Arachidonic acid ; Arteriosclerosis ; Atherosclerosis ; CD14 antigen ; CD36 antigen ; Cell activation ; Cytokines ; Eicosapentaenoic acid ; Femur ; Gas chromatography ; Granulocytes ; Inflammation ; Leukocytes (granulocytic) ; Leukotriene B4 ; Macrophages ; Monocytes ; Phenotypes ; Phosphatidylserine ; Phospholipids ; Plaques ; Plasma</subject><ispartof>Journal of extracellular vesicles, 2018-01, Vol.7, p.71-71</ispartof><rights>Copyright Taylor &amp; Francis Ltd. 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids></links><search><creatorcontrib>Sanden, Mathilde</creatorcontrib><creatorcontrib>Botha, Jaco</creatorcontrib><creatorcontrib>Nielsen, Michael René Skjelbo</creatorcontrib><creatorcontrib>Nielsen, Morten Hjuler</creatorcontrib><creatorcontrib>Schmidt, Erik Berg</creatorcontrib><creatorcontrib>Handberg, Aase</creatorcontrib><title>Atherosclerotic patients have lower levels of BLTR1 expressing microvesicles compared to healthy individuals</title><title>Journal of extracellular vesicles</title><description>Background: Monocytes/macrophages play a crucial role in the development, progression, and complication of atherosclerosis. In particular, foam cell formation driven by CD36 mediated internalisation of oxLDL leads to activation of monocytes and subsequent release of monocytederived microvesicles (MMVs). Further, pro-inflammatory leukotriene B4 derived from arachidonic acid (AA) promotes atherosclerosis through the high-affinity receptor BLTR1. Thus, we aimed to investigate the correlation between different MMV phenotypes on the one hand, and AA and eicosapentaenoic acid (EPA) contents in different compartments including atherosclerotic plaques, plasma and granulocytes on the other. This might elucidate the potential of CD36 and BLTR1 bearing MMV phenotypes as novel biomarkers in predicting atherosclerosis. Methods: Plasma samples from 48 subjects with femoral atherosclerosis and 24 healthy controls were analysed on an Apogee A60 MicroPLUS flow cytometer. Platelet-poor plasma was labelled with lactadherin-FITC, anti-CD14-APC, anti-CD36-PE and anti-BLTR1-AF700. MVs were defined as phosphatidylserine-exposing (PS+) events &lt;1000 nm in size. EPA and AA content in granulocytes, plasma phospholipids and atherosclerotic plaques were analysed using gas chromatography. Results: Patients with atherosclerosis had lower levels of BLTR1+ MVs (p = 0.007), CD14+BLTR1+ MVs (p = 0.007) and CD14+BLTR1+CD36+ MVs (p = 0.001) compared to healthy controls. Further, CD14+ MVs and CD14+CD36+ MVs correlated negatively with AA in granulocytes (r = -0.302, p = 0.039 and r = -0.322, p = 0.028, respectively). CD14 +CD36+ MVs correlated negatively with AA in plasma phospholipids (r = -0.315, p = 0.029). Lastly, CD14+ MVs and CD14+BLTR1+ MVs tended to correlate inversely with AA in plasma phospholipids and AA in atherosclerotic plaques, respectively (r = -0.284, p = 0.050 and r = - 0.291, p = 0.058). Summary/Conclusion: We demonstrated that atherosclerotic patients had lower levels of BLTR1+ MV phenotypes compared to healthy individuals. This is possibly caused by higher levels of LTB4 and inflammatory cytokines in patients which leads to receptor downregulation. Further investigations into the origin and phenotype may support the potential of circulating MVs in early diagnosis of atherosclerosis.</description><subject>Arachidonic acid</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>CD14 antigen</subject><subject>CD36 antigen</subject><subject>Cell activation</subject><subject>Cytokines</subject><subject>Eicosapentaenoic acid</subject><subject>Femur</subject><subject>Gas chromatography</subject><subject>Granulocytes</subject><subject>Inflammation</subject><subject>Leukocytes (granulocytic)</subject><subject>Leukotriene B4</subject><subject>Macrophages</subject><subject>Monocytes</subject><subject>Phenotypes</subject><subject>Phosphatidylserine</subject><subject>Phospholipids</subject><subject>Plaques</subject><subject>Plasma</subject><issn>2001-3078</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNjL0KwjAUhYMgKNp3uOAsJP7UZlRRHJzEXUJ7tSlpUnPTqG9vBh_AM5xv-A5nwMYLzsV8yTfFiGVEDU-RK7Eu5JiZbajROypN6qBL6FTQaANBrSKCcS_0YDCiIXB32J2vFwH47jwSafuAVpfeRSSdDghK13bKYwXBQY3KhPoD2lY66qpXhqZseE_A7McJmx0P1_1p3nn37JHCrXG9t0ndFkLkOZdSrpf_rb4rp0px</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>Sanden, Mathilde</creator><creator>Botha, Jaco</creator><creator>Nielsen, Michael René Skjelbo</creator><creator>Nielsen, Morten Hjuler</creator><creator>Schmidt, Erik Berg</creator><creator>Handberg, Aase</creator><general>John Wiley &amp; 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Calcified Tissue Abstracts</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Journal of extracellular vesicles</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sanden, Mathilde</au><au>Botha, Jaco</au><au>Nielsen, Michael René Skjelbo</au><au>Nielsen, Morten Hjuler</au><au>Schmidt, Erik Berg</au><au>Handberg, Aase</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Atherosclerotic patients have lower levels of BLTR1 expressing microvesicles compared to healthy individuals</atitle><jtitle>Journal of extracellular vesicles</jtitle><date>2018-01-01</date><risdate>2018</risdate><volume>7</volume><spage>71</spage><epage>71</epage><pages>71-71</pages><eissn>2001-3078</eissn><abstract>Background: Monocytes/macrophages play a crucial role in the development, progression, and complication of atherosclerosis. In particular, foam cell formation driven by CD36 mediated internalisation of oxLDL leads to activation of monocytes and subsequent release of monocytederived microvesicles (MMVs). Further, pro-inflammatory leukotriene B4 derived from arachidonic acid (AA) promotes atherosclerosis through the high-affinity receptor BLTR1. Thus, we aimed to investigate the correlation between different MMV phenotypes on the one hand, and AA and eicosapentaenoic acid (EPA) contents in different compartments including atherosclerotic plaques, plasma and granulocytes on the other. This might elucidate the potential of CD36 and BLTR1 bearing MMV phenotypes as novel biomarkers in predicting atherosclerosis. Methods: Plasma samples from 48 subjects with femoral atherosclerosis and 24 healthy controls were analysed on an Apogee A60 MicroPLUS flow cytometer. Platelet-poor plasma was labelled with lactadherin-FITC, anti-CD14-APC, anti-CD36-PE and anti-BLTR1-AF700. MVs were defined as phosphatidylserine-exposing (PS+) events &lt;1000 nm in size. EPA and AA content in granulocytes, plasma phospholipids and atherosclerotic plaques were analysed using gas chromatography. Results: Patients with atherosclerosis had lower levels of BLTR1+ MVs (p = 0.007), CD14+BLTR1+ MVs (p = 0.007) and CD14+BLTR1+CD36+ MVs (p = 0.001) compared to healthy controls. Further, CD14+ MVs and CD14+CD36+ MVs correlated negatively with AA in granulocytes (r = -0.302, p = 0.039 and r = -0.322, p = 0.028, respectively). CD14 +CD36+ MVs correlated negatively with AA in plasma phospholipids (r = -0.315, p = 0.029). Lastly, CD14+ MVs and CD14+BLTR1+ MVs tended to correlate inversely with AA in plasma phospholipids and AA in atherosclerotic plaques, respectively (r = -0.284, p = 0.050 and r = - 0.291, p = 0.058). Summary/Conclusion: We demonstrated that atherosclerotic patients had lower levels of BLTR1+ MV phenotypes compared to healthy individuals. This is possibly caused by higher levels of LTB4 and inflammatory cytokines in patients which leads to receptor downregulation. Further investigations into the origin and phenotype may support the potential of circulating MVs in early diagnosis of atherosclerosis.</abstract><cop>Abingdon</cop><pub>John Wiley &amp; Sons, Inc</pub></addata></record>
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subjects Arachidonic acid
Arteriosclerosis
Atherosclerosis
CD14 antigen
CD36 antigen
Cell activation
Cytokines
Eicosapentaenoic acid
Femur
Gas chromatography
Granulocytes
Inflammation
Leukocytes (granulocytic)
Leukotriene B4
Macrophages
Monocytes
Phenotypes
Phosphatidylserine
Phospholipids
Plaques
Plasma
title Atherosclerotic patients have lower levels of BLTR1 expressing microvesicles compared to healthy individuals
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