Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation

Purpose Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are...

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Veröffentlicht in:Sleep & breathing 2020-12, Vol.24 (4), p.1463-1472
Hauptverfasser: Freitas, Lunara S., Silveira, André C., Martins, Franco C., Costa-Hong, Valéria, Lebkuchen, Adriana, Cardozo, Karina H. M., Bernardes, Fernanda M., Bortolotto, Luiz A., Lorenzi-Filho, Geraldo, Oliveira, Edilamar M., Drager, Luciano F.
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container_end_page 1472
container_issue 4
container_start_page 1463
container_title Sleep & breathing
container_volume 24
creator Freitas, Lunara S.
Silveira, André C.
Martins, Franco C.
Costa-Hong, Valéria
Lebkuchen, Adriana
Cardozo, Karina H. M.
Bernardes, Fernanda M.
Bortolotto, Luiz A.
Lorenzi-Filho, Geraldo
Oliveira, Edilamar M.
Drager, Luciano F.
description Purpose Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. Methods We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group ( n  = 6), mild OSA group ( n  = 12), moderate OSA group ( n  = 15), and severe OSA group ( n  = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). Results The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 ( ß  = 68.4; EP = 29.8; p  = 0.02) and miR-320e ( ß  = 76.1; EP = 31.3; p  = 0.02). Conclusion Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.
doi_str_mv 10.1007/s11325-019-02003-1
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M. ; Bernardes, Fernanda M. ; Bortolotto, Luiz A. ; Lorenzi-Filho, Geraldo ; Oliveira, Edilamar M. ; Drager, Luciano F.</creator><creatorcontrib>Freitas, Lunara S. ; Silveira, André C. ; Martins, Franco C. ; Costa-Hong, Valéria ; Lebkuchen, Adriana ; Cardozo, Karina H. M. ; Bernardes, Fernanda M. ; Bortolotto, Luiz A. ; Lorenzi-Filho, Geraldo ; Oliveira, Edilamar M. ; Drager, Luciano F.</creatorcontrib><description>Purpose Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. Methods We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group ( n  = 6), mild OSA group ( n  = 12), moderate OSA group ( n  = 15), and severe OSA group ( n  = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). Results The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 ( ß  = 68.4; EP = 29.8; p  = 0.02) and miR-320e ( ß  = 76.1; EP = 31.3; p  = 0.02). Conclusion Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.</description><identifier>ISSN: 1520-9512</identifier><identifier>EISSN: 1522-1709</identifier><identifier>DOI: 10.1007/s11325-019-02003-1</identifier><identifier>PMID: 31898194</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Apnea ; Body fat ; Body mass index ; Body weight ; Cancer ; Cardiovascular diseases ; Cell proliferation ; Congestive heart failure ; Dentistry ; DNA microarrays ; Gene expression ; Heart failure ; Internal Medicine ; Ischemia ; Medicine ; Medicine &amp; Public Health ; MicroRNAs ; miRNA ; Myocardial ischemia ; Neurology ; Nucleotides ; Otorhinolaryngology ; Overweight ; Pediatrics ; Pneumology/Respiratory System ; Polymerase chain reaction ; Reperfusion ; Sleep ; Sleep apnea ; Sleep Breathing Physiology and Disorders • Original Article ; Sleep disorders</subject><ispartof>Sleep &amp; breathing, 2020-12, Vol.24 (4), p.1463-1472</ispartof><rights>Springer Nature Switzerland AG 2020</rights><rights>Springer Nature Switzerland AG 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-d055d0b0d8c8adfcae7e15877fec9fbb2fce33ddbe6a9bc308fe73f1d3a0d01b3</citedby><cites>FETCH-LOGICAL-c375t-d055d0b0d8c8adfcae7e15877fec9fbb2fce33ddbe6a9bc308fe73f1d3a0d01b3</cites><orcidid>0000-0002-0556-4986</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/s11325-019-02003-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11325-019-02003-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31898194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Freitas, Lunara S.</creatorcontrib><creatorcontrib>Silveira, André C.</creatorcontrib><creatorcontrib>Martins, Franco C.</creatorcontrib><creatorcontrib>Costa-Hong, Valéria</creatorcontrib><creatorcontrib>Lebkuchen, Adriana</creatorcontrib><creatorcontrib>Cardozo, Karina H. M.</creatorcontrib><creatorcontrib>Bernardes, Fernanda M.</creatorcontrib><creatorcontrib>Bortolotto, Luiz A.</creatorcontrib><creatorcontrib>Lorenzi-Filho, Geraldo</creatorcontrib><creatorcontrib>Oliveira, Edilamar M.</creatorcontrib><creatorcontrib>Drager, Luciano F.</creatorcontrib><title>Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation</title><title>Sleep &amp; breathing</title><addtitle>Sleep Breath</addtitle><addtitle>Sleep Breath</addtitle><description>Purpose Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. Methods We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group ( n  = 6), mild OSA group ( n  = 12), moderate OSA group ( n  = 15), and severe OSA group ( n  = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). Results The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 ( ß  = 68.4; EP = 29.8; p  = 0.02) and miR-320e ( ß  = 76.1; EP = 31.3; p  = 0.02). Conclusion Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.</description><subject>Apnea</subject><subject>Body fat</subject><subject>Body mass index</subject><subject>Body weight</subject><subject>Cancer</subject><subject>Cardiovascular diseases</subject><subject>Cell proliferation</subject><subject>Congestive heart failure</subject><subject>Dentistry</subject><subject>DNA microarrays</subject><subject>Gene expression</subject><subject>Heart failure</subject><subject>Internal Medicine</subject><subject>Ischemia</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Myocardial ischemia</subject><subject>Neurology</subject><subject>Nucleotides</subject><subject>Otorhinolaryngology</subject><subject>Overweight</subject><subject>Pediatrics</subject><subject>Pneumology/Respiratory System</subject><subject>Polymerase chain reaction</subject><subject>Reperfusion</subject><subject>Sleep</subject><subject>Sleep apnea</subject><subject>Sleep Breathing Physiology and Disorders • Original Article</subject><subject>Sleep disorders</subject><issn>1520-9512</issn><issn>1522-1709</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp9kc9u1DAQhyNERUvhBTggS1w4NGXG3mySY1WVP1JFpQJna2KPu66SeLGdoj4Fr4y7W0DiwGkszTffjPyrqlcIpwjQvkuISjY1YF-DBFA1PqmOsJGyxhb6p7s31H2D8rB6ntItAK66Hp9Vhwq7vsN-dVT9_MJ3HFmEIeW4mOzvWKSReStoOzMJnwSlFIynzFb88HkjjI9mGSn7-UZM3sRw_fksicjjDslBbJhiFo78uEQ-EdN9MBStp7HYzIYnTyeCZisMzYaj2MYwesexGMP8ojpwNCZ--ViPq2_vL76ef6wvrz58Oj-7rI1qm1xbaBoLA9jOdGSdIW4Zm65tHZveDYN0hpWyduA19YNR0DlulUOrCCzgoI6rt3tv2f594ZT1VI7jcaSZw5K0VEqtEVfrdUHf_IPehiXO5TotV-0DB7IvlNxT5UNSiuz0NvqJ4r1G0A9x6X1cusSld3FpLEOvH9XLMLH9M_I7nwKoPZBKa77h-Hf3f7S_AE38o_w</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Freitas, Lunara S.</creator><creator>Silveira, André C.</creator><creator>Martins, Franco C.</creator><creator>Costa-Hong, Valéria</creator><creator>Lebkuchen, Adriana</creator><creator>Cardozo, Karina H. 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M.</creatorcontrib><creatorcontrib>Bernardes, Fernanda M.</creatorcontrib><creatorcontrib>Bortolotto, Luiz A.</creatorcontrib><creatorcontrib>Lorenzi-Filho, Geraldo</creatorcontrib><creatorcontrib>Oliveira, Edilamar M.</creatorcontrib><creatorcontrib>Drager, Luciano F.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Social Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Social 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><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Sleep &amp; breathing</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Freitas, Lunara S.</au><au>Silveira, André C.</au><au>Martins, Franco C.</au><au>Costa-Hong, Valéria</au><au>Lebkuchen, Adriana</au><au>Cardozo, Karina H. M.</au><au>Bernardes, Fernanda M.</au><au>Bortolotto, Luiz A.</au><au>Lorenzi-Filho, Geraldo</au><au>Oliveira, Edilamar M.</au><au>Drager, Luciano F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation</atitle><jtitle>Sleep &amp; breathing</jtitle><stitle>Sleep Breath</stitle><addtitle>Sleep Breath</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>24</volume><issue>4</issue><spage>1463</spage><epage>1472</epage><pages>1463-1472</pages><issn>1520-9512</issn><eissn>1522-1709</eissn><abstract>Purpose Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. Methods We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group ( n  = 6), mild OSA group ( n  = 12), moderate OSA group ( n  = 15), and severe OSA group ( n  = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). Results The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 ( ß  = 68.4; EP = 29.8; p  = 0.02) and miR-320e ( ß  = 76.1; EP = 31.3; p  = 0.02). Conclusion Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>31898194</pmid><doi>10.1007/s11325-019-02003-1</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0556-4986</orcidid></addata></record>
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subjects Apnea
Body fat
Body mass index
Body weight
Cancer
Cardiovascular diseases
Cell proliferation
Congestive heart failure
Dentistry
DNA microarrays
Gene expression
Heart failure
Internal Medicine
Ischemia
Medicine
Medicine & Public Health
MicroRNAs
miRNA
Myocardial ischemia
Neurology
Nucleotides
Otorhinolaryngology
Overweight
Pediatrics
Pneumology/Respiratory System
Polymerase chain reaction
Reperfusion
Sleep
Sleep apnea
Sleep Breathing Physiology and Disorders • Original Article
Sleep disorders
title Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation
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