Atrial natriuretic peptide is negatively regulated by microRNA-425
Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with bloo...
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Veröffentlicht in: | The Journal of clinical investigation 2013-08, Vol.123 (8), p.3378-3382 |
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creator | Arora, Pankaj Wu, Connie Khan, Abigail May Bloch, Donald B Davis-Dusenbery, Brandi N Ghorbani, Anahita Spagnolli, Ester Martinez, Andrew Ryan, Allicia Tainsh, Laurel T Kim, Samuel Rong, Jian Huan, Tianxiao Freedman, Jane E Levy, Daniel Miller, Karen K Hata, Akiko Del Monte, Federica Vandenwijngaert, Sara Swinnen, Melissa Janssens, Stefan Holmes, Tara M Buys, Emmanuel S Bloch, Kenneth D Newton-Cheh, Christopher Wang, Thomas J |
description | Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure. |
doi_str_mv | 10.1172/JCI67383 |
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Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI67383</identifier><identifier>PMID: 23867623</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>3' Untranslated Regions ; Adult ; Animals ; Atrial Natriuretic Factor - blood ; Atrial Natriuretic Factor - genetics ; Biomedical research ; Blood pressure ; Brief Report ; Cardiovascular disease ; Care and treatment ; Cercopithecus aethiops ; COS Cells ; Cyclic GMP - blood ; Diet ; Female ; Gene expression ; Gene Expression - drug effects ; Gene Frequency ; Genealogy ; Genetic aspects ; Genetic Association Studies ; Genetic variation ; Genotype & phenotype ; Heart failure ; Humans ; Hypertension ; Hypertension - blood ; Hypertension - genetics ; Male ; MicroRNA ; MicroRNAs - genetics ; Natriuretic peptides ; Nutrition research ; Peptides ; Polymorphism, Single Nucleotide ; RNA Interference ; Sequence Analysis, DNA ; Sodium Chloride, Dietary - pharmacology ; Studies ; Young Adult</subject><ispartof>The Journal of clinical investigation, 2013-08, Vol.123 (8), p.3378-3382</ispartof><rights>COPYRIGHT 2013 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Aug 2013</rights><rights>Copyright © 2013, American Society for Clinical Investigation 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c703t-808052953cabb84c87676dc7485fbf5263c9b70f446dc9c72a1098edcae2f23c3</citedby><cites>FETCH-LOGICAL-c703t-808052953cabb84c87676dc7485fbf5263c9b70f446dc9c72a1098edcae2f23c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726159/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726159/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23867623$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arora, Pankaj</creatorcontrib><creatorcontrib>Wu, Connie</creatorcontrib><creatorcontrib>Khan, Abigail May</creatorcontrib><creatorcontrib>Bloch, Donald B</creatorcontrib><creatorcontrib>Davis-Dusenbery, Brandi N</creatorcontrib><creatorcontrib>Ghorbani, Anahita</creatorcontrib><creatorcontrib>Spagnolli, Ester</creatorcontrib><creatorcontrib>Martinez, Andrew</creatorcontrib><creatorcontrib>Ryan, Allicia</creatorcontrib><creatorcontrib>Tainsh, Laurel T</creatorcontrib><creatorcontrib>Kim, Samuel</creatorcontrib><creatorcontrib>Rong, Jian</creatorcontrib><creatorcontrib>Huan, Tianxiao</creatorcontrib><creatorcontrib>Freedman, Jane E</creatorcontrib><creatorcontrib>Levy, Daniel</creatorcontrib><creatorcontrib>Miller, Karen K</creatorcontrib><creatorcontrib>Hata, Akiko</creatorcontrib><creatorcontrib>Del Monte, Federica</creatorcontrib><creatorcontrib>Vandenwijngaert, Sara</creatorcontrib><creatorcontrib>Swinnen, Melissa</creatorcontrib><creatorcontrib>Janssens, Stefan</creatorcontrib><creatorcontrib>Holmes, Tara M</creatorcontrib><creatorcontrib>Buys, Emmanuel S</creatorcontrib><creatorcontrib>Bloch, Kenneth D</creatorcontrib><creatorcontrib>Newton-Cheh, Christopher</creatorcontrib><creatorcontrib>Wang, Thomas J</creatorcontrib><title>Atrial natriuretic peptide is negatively regulated by microRNA-425</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.</description><subject>3' Untranslated Regions</subject><subject>Adult</subject><subject>Animals</subject><subject>Atrial Natriuretic Factor - blood</subject><subject>Atrial Natriuretic Factor - genetics</subject><subject>Biomedical research</subject><subject>Blood pressure</subject><subject>Brief Report</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Cyclic GMP - blood</subject><subject>Diet</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Gene Frequency</subject><subject>Genealogy</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies</subject><subject>Genetic variation</subject><subject>Genotype & phenotype</subject><subject>Heart failure</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - blood</subject><subject>Hypertension - genetics</subject><subject>Male</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>Natriuretic peptides</subject><subject>Nutrition research</subject><subject>Peptides</subject><subject>Polymorphism, Single Nucleotide</subject><subject>RNA Interference</subject><subject>Sequence Analysis, DNA</subject><subject>Sodium Chloride, Dietary - pharmacology</subject><subject>Studies</subject><subject>Young Adult</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkttq3DAQhk1paTZpoU9QDIXSXjjV0ZJvAtulhy2hgfRwK2Tt2KvglbeWHLJv3wndpHHZi6KLgZlPv0Yzf5a9oOSUUsXefVksS8U1f5TNqJS60Izrx9mMEEaLCgtH2XGMV4RQIaR4mh1huVQl47Ps_TwN3nZ5sBjHAZJ3-Ra2ya8g9zEP0Nrkr6Hb5QO0Y2cTrPJ6l2-8G_rLr_NCMPkse9LYLsLzfTzJfnz88H3xuTi_-LRczM8LpwhPhSaaSFZJ7mxda-G0whZWTgktm7qRrOSuqhVphMBs5RSzlFQaVs4Caxh3_CQ7-6O7HesN5iGkwXZmO_iNHXamt95MK8GvTdtfG65YSWWFAm_2AkP_a4SYzMZHB11nA_RjNFRwQThhvET01T_oVT8OAb-HFNMVDo9Wf6nWdmB8aHp8192KmjkXCCjJKVLFAaqFANhkH6DxmJ7wpwd4PCvAsR-88HZyAZkEN6m1Y4xm-e3y_9mLn1P29QN2DbZL69h3Y_J9iFNwP1g0RYwDNPdLocTcGtTcGRTRlw-XeA_eOZL_Bvuf2mc</recordid><startdate>20130801</startdate><enddate>20130801</enddate><creator>Arora, Pankaj</creator><creator>Wu, Connie</creator><creator>Khan, Abigail 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natriuretic peptide is negatively regulated by microRNA-425</title><author>Arora, Pankaj ; Wu, Connie ; Khan, Abigail May ; Bloch, Donald B ; Davis-Dusenbery, Brandi N ; Ghorbani, Anahita ; Spagnolli, Ester ; Martinez, Andrew ; Ryan, Allicia ; Tainsh, Laurel T ; Kim, Samuel ; Rong, Jian ; Huan, Tianxiao ; Freedman, Jane E ; Levy, Daniel ; Miller, Karen K ; Hata, Akiko ; Del Monte, Federica ; Vandenwijngaert, Sara ; Swinnen, Melissa ; Janssens, Stefan ; Holmes, Tara M ; Buys, Emmanuel S ; Bloch, Kenneth D ; Newton-Cheh, Christopher ; Wang, Thomas J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c703t-808052953cabb84c87676dc7485fbf5263c9b70f446dc9c72a1098edcae2f23c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3' Untranslated Regions</topic><topic>Adult</topic><topic>Animals</topic><topic>Atrial Natriuretic Factor - blood</topic><topic>Atrial Natriuretic Factor - genetics</topic><topic>Biomedical research</topic><topic>Blood pressure</topic><topic>Brief Report</topic><topic>Cardiovascular disease</topic><topic>Care and treatment</topic><topic>Cercopithecus aethiops</topic><topic>COS Cells</topic><topic>Cyclic GMP - blood</topic><topic>Diet</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Gene Frequency</topic><topic>Genealogy</topic><topic>Genetic aspects</topic><topic>Genetic Association Studies</topic><topic>Genetic variation</topic><topic>Genotype & phenotype</topic><topic>Heart failure</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - blood</topic><topic>Hypertension - genetics</topic><topic>Male</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>Natriuretic peptides</topic><topic>Nutrition research</topic><topic>Peptides</topic><topic>Polymorphism, Single Nucleotide</topic><topic>RNA Interference</topic><topic>Sequence Analysis, 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negatively regulated by microRNA-425</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2013-08-01</date><risdate>2013</risdate><volume>123</volume><issue>8</issue><spage>3378</spage><epage>3382</epage><pages>3378-3382</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>23867623</pmid><doi>10.1172/JCI67383</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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source | Journals@Ovid Ovid Autoload; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
subjects | 3' Untranslated Regions Adult Animals Atrial Natriuretic Factor - blood Atrial Natriuretic Factor - genetics Biomedical research Blood pressure Brief Report Cardiovascular disease Care and treatment Cercopithecus aethiops COS Cells Cyclic GMP - blood Diet Female Gene expression Gene Expression - drug effects Gene Frequency Genealogy Genetic aspects Genetic Association Studies Genetic variation Genotype & phenotype Heart failure Humans Hypertension Hypertension - blood Hypertension - genetics Male MicroRNA MicroRNAs - genetics Natriuretic peptides Nutrition research Peptides Polymorphism, Single Nucleotide RNA Interference Sequence Analysis, DNA Sodium Chloride, Dietary - pharmacology Studies Young Adult |
title | Atrial natriuretic peptide is negatively regulated by microRNA-425 |
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