Altered Extracellular Vesicle MicroRNA Expression in Ischemic Stroke and Small Vessel Disease
Active transport of microRNAs (miRNA) in extracellular vesicles (EV) occurs in disease. Circulating EV-packaged miRNAs in the serum of stroke patients were compared to stroke mimics with matched cardio- and cerebrovascular risk factors, with corroboration of results in a pre-clinical model. An unbia...
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| Veröffentlicht in: | Translational stroke research 2019-10, Vol.10 (5), p.495-508 |
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| creator | van Kralingen, Josie C. McFall, Aisling Ord, Emily N. J. Coyle, Thomas F. Bissett, Maria McClure, John D. McCabe, Christopher Macrae, I. Mhairi Dawson, Jesse Work, Lorraine M. |
| description | Active transport of microRNAs (miRNA) in extracellular vesicles (EV) occurs in disease. Circulating EV-packaged miRNAs in the serum of stroke patients were compared to stroke mimics with matched cardio- and cerebrovascular risk factors, with corroboration of results in a pre-clinical model. An unbiased miRNA microarray was performed in stroke vs. stroke mimic patients (
n
= 39). Results were validated (
n
= 173 patients) by real-time quantitative polymerase chain reaction. miRNA expression was quantified in total serum/EV (
n
= 5–7) of naïve adult spontaneously hypertensive stroke-prone rats (SHRSP), their normotensive reference strain (Wistar Kyoto, WKY) and in circulating EV (
n
= 3), peri-infarct brain (
n
= 6), or EV derived from this region (
n
= 3) in SHRSP following transient middle cerebral artery occlusion (tMCAO). Circulating EV concentration did not differ between stroke and stroke mimic patients. The microarray identified many altered EV-packaged miRNAs: levels of miRNA-17-5p, -20b-5p and -93-5p (miRNA-17 family members) and miRNA-27b-3p were significantly (
p
≤ 0.05) increased in stroke vs. stroke mimic patients. Patients with small vessel disease (SVD) consistently had the highest miRNA levels. Circulating EV concentration was unaltered between naïve SHRSP and WKY but levels of miRNA-17-5p and -93-5p were significantly increased in SHRSP. tMCAO in SHRSP did not further alter circulating EV miRNA-17 family member expression and nor did it change total miRNA-17 family levels in peri-infarct brain tissue or in EV isolated from this region at 24 h post-tMCAO. Changes in EV packaged miRNA expression was validated in patients with stroke, particularly those with SVD and corroborated pre-clinically. Together, altered circulating EV levels of miRNA-17 family members may reflect the chronic sequelae underlying cerebrovascular SVD rather than the acute ischemic stroke itself. |
| doi_str_mv | 10.1007/s12975-018-0682-3 |
| format | Article |
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n
= 39). Results were validated (
n
= 173 patients) by real-time quantitative polymerase chain reaction. miRNA expression was quantified in total serum/EV (
n
= 5–7) of naïve adult spontaneously hypertensive stroke-prone rats (SHRSP), their normotensive reference strain (Wistar Kyoto, WKY) and in circulating EV (
n
= 3), peri-infarct brain (
n
= 6), or EV derived from this region (
n
= 3) in SHRSP following transient middle cerebral artery occlusion (tMCAO). Circulating EV concentration did not differ between stroke and stroke mimic patients. The microarray identified many altered EV-packaged miRNAs: levels of miRNA-17-5p, -20b-5p and -93-5p (miRNA-17 family members) and miRNA-27b-3p were significantly (
p
≤ 0.05) increased in stroke vs. stroke mimic patients. Patients with small vessel disease (SVD) consistently had the highest miRNA levels. Circulating EV concentration was unaltered between naïve SHRSP and WKY but levels of miRNA-17-5p and -93-5p were significantly increased in SHRSP. tMCAO in SHRSP did not further alter circulating EV miRNA-17 family member expression and nor did it change total miRNA-17 family levels in peri-infarct brain tissue or in EV isolated from this region at 24 h post-tMCAO. Changes in EV packaged miRNA expression was validated in patients with stroke, particularly those with SVD and corroborated pre-clinically. Together, altered circulating EV levels of miRNA-17 family members may reflect the chronic sequelae underlying cerebrovascular SVD rather than the acute ischemic stroke itself.</description><identifier>ISSN: 1868-4483</identifier><identifier>EISSN: 1868-601X</identifier><identifier>DOI: 10.1007/s12975-018-0682-3</identifier><identifier>PMID: 30617992</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Biomedical and Life Sciences ; Biomedicine ; Brain Ischemia - blood ; Brain research ; Cardiology ; Cerebral Small Vessel Diseases - blood ; Disease Models, Animal ; Extracellular Vesicles - metabolism ; Genes ; Ischemia ; Male ; MicroRNAs ; MicroRNAs - blood ; Neurology ; Neurosciences ; Neurosurgery ; Original ; Original Article ; Patients ; Rats, Inbred SHR ; Rats, Inbred WKY ; Software ; Statistical analysis ; Stroke ; Stroke - blood ; Stroke - complications ; Thermal cycling ; Validation studies ; Vascular Surgery ; Veins & arteries</subject><ispartof>Translational stroke research, 2019-10, Vol.10 (5), p.495-508</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-e9a7ac081b6f0b08a56a8ed3e44956c5df1a7283155a7fc43b48b38e440dbe113</citedby><cites>FETCH-LOGICAL-c470t-e9a7ac081b6f0b08a56a8ed3e44956c5df1a7283155a7fc43b48b38e440dbe113</cites><orcidid>0000-0002-6462-4109</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12975-018-0682-3$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2920241253?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,21388,21389,27924,27925,33530,33531,33744,33745,41488,42557,43659,43805,51319,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30617992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Kralingen, Josie C.</creatorcontrib><creatorcontrib>McFall, Aisling</creatorcontrib><creatorcontrib>Ord, Emily N. J.</creatorcontrib><creatorcontrib>Coyle, Thomas F.</creatorcontrib><creatorcontrib>Bissett, Maria</creatorcontrib><creatorcontrib>McClure, John D.</creatorcontrib><creatorcontrib>McCabe, Christopher</creatorcontrib><creatorcontrib>Macrae, I. Mhairi</creatorcontrib><creatorcontrib>Dawson, Jesse</creatorcontrib><creatorcontrib>Work, Lorraine M.</creatorcontrib><title>Altered Extracellular Vesicle MicroRNA Expression in Ischemic Stroke and Small Vessel Disease</title><title>Translational stroke research</title><addtitle>Transl. Stroke Res</addtitle><addtitle>Transl Stroke Res</addtitle><description>Active transport of microRNAs (miRNA) in extracellular vesicles (EV) occurs in disease. Circulating EV-packaged miRNAs in the serum of stroke patients were compared to stroke mimics with matched cardio- and cerebrovascular risk factors, with corroboration of results in a pre-clinical model. An unbiased miRNA microarray was performed in stroke vs. stroke mimic patients (
n
= 39). Results were validated (
n
= 173 patients) by real-time quantitative polymerase chain reaction. miRNA expression was quantified in total serum/EV (
n
= 5–7) of naïve adult spontaneously hypertensive stroke-prone rats (SHRSP), their normotensive reference strain (Wistar Kyoto, WKY) and in circulating EV (
n
= 3), peri-infarct brain (
n
= 6), or EV derived from this region (
n
= 3) in SHRSP following transient middle cerebral artery occlusion (tMCAO). Circulating EV concentration did not differ between stroke and stroke mimic patients. The microarray identified many altered EV-packaged miRNAs: levels of miRNA-17-5p, -20b-5p and -93-5p (miRNA-17 family members) and miRNA-27b-3p were significantly (
p
≤ 0.05) increased in stroke vs. stroke mimic patients. Patients with small vessel disease (SVD) consistently had the highest miRNA levels. Circulating EV concentration was unaltered between naïve SHRSP and WKY but levels of miRNA-17-5p and -93-5p were significantly increased in SHRSP. tMCAO in SHRSP did not further alter circulating EV miRNA-17 family member expression and nor did it change total miRNA-17 family levels in peri-infarct brain tissue or in EV isolated from this region at 24 h post-tMCAO. Changes in EV packaged miRNA expression was validated in patients with stroke, particularly those with SVD and corroborated pre-clinically. Together, altered circulating EV levels of miRNA-17 family members may reflect the chronic sequelae underlying cerebrovascular SVD rather than the acute ischemic stroke itself.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain Ischemia - blood</subject><subject>Brain research</subject><subject>Cardiology</subject><subject>Cerebral Small Vessel Diseases - blood</subject><subject>Disease Models, Animal</subject><subject>Extracellular Vesicles - metabolism</subject><subject>Genes</subject><subject>Ischemia</subject><subject>Male</subject><subject>MicroRNAs</subject><subject>MicroRNAs - blood</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Neurosurgery</subject><subject>Original</subject><subject>Original Article</subject><subject>Patients</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Inbred WKY</subject><subject>Software</subject><subject>Statistical analysis</subject><subject>Stroke</subject><subject>Stroke - blood</subject><subject>Stroke - complications</subject><subject>Thermal cycling</subject><subject>Validation studies</subject><subject>Vascular Surgery</subject><subject>Veins & arteries</subject><issn>1868-4483</issn><issn>1868-601X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1UU1rFTEUDaLYUvsD3EjAjZuxuUkmk9kIj7bWQqtgW3EjIZO506ZmZp7JTNF_3wzvtX6A2SRwPm7OPYS8BPYWGKsOEvC6KgsGumBK80I8IbuglS4Ug69Pt28ptdgh-yndsnwESCXFc7IjmIKqrvku-bYKE0Zs6fHPKVqHIczBRvoFk3cB6bl3cfz8cZXhdcSU_DhQP9DT5G6w945eTHH8jtQOLb3obQiLMGGgRz6hTfiCPOtsSLi_vffI1fvjy8MPxdmnk9PD1VnhZMWmAmtbWcc0NKpjDdO2VFZjK1DKulSubDuwFdcCytJWnZOikboROsOsbRBA7JF3G9_13PTYOhxymGDW0fc2_jKj9eZvZPA35nq8M6oSQoPIBm-2BnH8MWOaTO_Tsg074Dgnw0GVrK614pn6-h_q7TjHIcczvOaMS-DlYggbVt5fShG7x88AM0t_ZtOfyf2ZpT-zaF79meJR8dBWJvANIWVouMb4e_T_Xe8BRx6mGg</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>van Kralingen, Josie C.</creator><creator>McFall, Aisling</creator><creator>Ord, Emily N. J.</creator><creator>Coyle, Thomas F.</creator><creator>Bissett, Maria</creator><creator>McClure, John D.</creator><creator>McCabe, Christopher</creator><creator>Macrae, I. Mhairi</creator><creator>Dawson, Jesse</creator><creator>Work, Lorraine M.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6462-4109</orcidid></search><sort><creationdate>20191001</creationdate><title>Altered Extracellular Vesicle MicroRNA Expression in Ischemic Stroke and Small Vessel Disease</title><author>van Kralingen, Josie C. ; McFall, Aisling ; Ord, Emily N. J. ; Coyle, Thomas F. ; Bissett, Maria ; McClure, John D. ; McCabe, Christopher ; Macrae, I. Mhairi ; Dawson, Jesse ; Work, Lorraine M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-e9a7ac081b6f0b08a56a8ed3e44956c5df1a7283155a7fc43b48b38e440dbe113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain Ischemia - blood</topic><topic>Brain research</topic><topic>Cardiology</topic><topic>Cerebral Small Vessel Diseases - blood</topic><topic>Disease Models, Animal</topic><topic>Extracellular Vesicles - metabolism</topic><topic>Genes</topic><topic>Ischemia</topic><topic>Male</topic><topic>MicroRNAs</topic><topic>MicroRNAs - blood</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Neurosurgery</topic><topic>Original</topic><topic>Original Article</topic><topic>Patients</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Inbred WKY</topic><topic>Software</topic><topic>Statistical analysis</topic><topic>Stroke</topic><topic>Stroke - blood</topic><topic>Stroke - complications</topic><topic>Thermal cycling</topic><topic>Validation studies</topic><topic>Vascular Surgery</topic><topic>Veins & arteries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Kralingen, Josie C.</creatorcontrib><creatorcontrib>McFall, Aisling</creatorcontrib><creatorcontrib>Ord, Emily N. J.</creatorcontrib><creatorcontrib>Coyle, Thomas F.</creatorcontrib><creatorcontrib>Bissett, Maria</creatorcontrib><creatorcontrib>McClure, John D.</creatorcontrib><creatorcontrib>McCabe, Christopher</creatorcontrib><creatorcontrib>Macrae, I. Mhairi</creatorcontrib><creatorcontrib>Dawson, Jesse</creatorcontrib><creatorcontrib>Work, Lorraine M.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</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 One Psychology</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Translational stroke research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Kralingen, Josie C.</au><au>McFall, Aisling</au><au>Ord, Emily N. J.</au><au>Coyle, Thomas F.</au><au>Bissett, Maria</au><au>McClure, John D.</au><au>McCabe, Christopher</au><au>Macrae, I. Mhairi</au><au>Dawson, Jesse</au><au>Work, Lorraine M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered Extracellular Vesicle MicroRNA Expression in Ischemic Stroke and Small Vessel Disease</atitle><jtitle>Translational stroke research</jtitle><stitle>Transl. Stroke Res</stitle><addtitle>Transl Stroke Res</addtitle><date>2019-10-01</date><risdate>2019</risdate><volume>10</volume><issue>5</issue><spage>495</spage><epage>508</epage><pages>495-508</pages><issn>1868-4483</issn><eissn>1868-601X</eissn><abstract>Active transport of microRNAs (miRNA) in extracellular vesicles (EV) occurs in disease. Circulating EV-packaged miRNAs in the serum of stroke patients were compared to stroke mimics with matched cardio- and cerebrovascular risk factors, with corroboration of results in a pre-clinical model. An unbiased miRNA microarray was performed in stroke vs. stroke mimic patients (
n
= 39). Results were validated (
n
= 173 patients) by real-time quantitative polymerase chain reaction. miRNA expression was quantified in total serum/EV (
n
= 5–7) of naïve adult spontaneously hypertensive stroke-prone rats (SHRSP), their normotensive reference strain (Wistar Kyoto, WKY) and in circulating EV (
n
= 3), peri-infarct brain (
n
= 6), or EV derived from this region (
n
= 3) in SHRSP following transient middle cerebral artery occlusion (tMCAO). Circulating EV concentration did not differ between stroke and stroke mimic patients. The microarray identified many altered EV-packaged miRNAs: levels of miRNA-17-5p, -20b-5p and -93-5p (miRNA-17 family members) and miRNA-27b-3p were significantly (
p
≤ 0.05) increased in stroke vs. stroke mimic patients. Patients with small vessel disease (SVD) consistently had the highest miRNA levels. Circulating EV concentration was unaltered between naïve SHRSP and WKY but levels of miRNA-17-5p and -93-5p were significantly increased in SHRSP. tMCAO in SHRSP did not further alter circulating EV miRNA-17 family member expression and nor did it change total miRNA-17 family levels in peri-infarct brain tissue or in EV isolated from this region at 24 h post-tMCAO. Changes in EV packaged miRNA expression was validated in patients with stroke, particularly those with SVD and corroborated pre-clinically. Together, altered circulating EV levels of miRNA-17 family members may reflect the chronic sequelae underlying cerebrovascular SVD rather than the acute ischemic stroke itself.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30617992</pmid><doi>10.1007/s12975-018-0682-3</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-6462-4109</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biomedical and Life Sciences Biomedicine Brain Ischemia - blood Brain research Cardiology Cerebral Small Vessel Diseases - blood Disease Models, Animal Extracellular Vesicles - metabolism Genes Ischemia Male MicroRNAs MicroRNAs - blood Neurology Neurosciences Neurosurgery Original Original Article Patients Rats, Inbred SHR Rats, Inbred WKY Software Statistical analysis Stroke Stroke - blood Stroke - complications Thermal cycling Validation studies Vascular Surgery Veins & arteries |
| title | Altered Extracellular Vesicle MicroRNA Expression in Ischemic Stroke and Small Vessel Disease |
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