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Antisense regulatio...
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Celik, SelviLund University,Lunds universitet,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,Cardiovascular Epigenetics,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine
(författare)
Antisense regulation of atrial natriuretic peptide expression
- Artikel/kapitelEngelska2019
Förlag, utgivningsår, omfång ...
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2019-10-03
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American Society for Clinical Investigation,2019
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:3e98045f-a6f0-4e47-8d65-a49af1d4922f
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https://lup.lub.lu.se/record/3e98045f-a6f0-4e47-8d65-a49af1d4922fURI
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https://doi.org/10.1172/jci.insight.130978DOI
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Språk:engelska
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Sammanfattning på:engelska
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The cardiac hormone atrial natriuretic peptide (ANP) is a central regulator of blood volume and a therapeutic target in hypertension and heart failure. Enhanced ANP activity in such conditions through inhibition of the degradative enzyme neprilysin has shown clinical efficacy but is complicated by consequences of simultaneous accumulation of a heterogeneous array of other hormones. Targets for specific ANP enhancement have not been available. Here, we describe a cis-acting antisense transcript (NPPA-AS1), which negatively regulates ANP expression in human cardiomyocytes. We show that NPPA-AS1 regulates ANP expression via facilitating NPPA repressor RE1-silencing transcription factor (REST) binding to its promoter, rather than forming an RNA duplex with ANP mRNA. Expression of ANP mRNA and NPPA-AS1 was increased and correlated in isolated strained human cardiomyocytes and in hearts from patients with advanced heart failure. Further, inhibition of NPPA-AS1 in vitro and in vivo resulted in increased myocardial expression of ANP, increased circulating ANP, increased renal cGMP, and lower blood pressure. The effects of NPPA-AS1 inhibition on NPPA expression in human cardiomyocytes were further marked under cell-strain conditions. Collectively, these results implicate the antisense transcript NPPA-AS1 as part of a physiologic self-regulatory ANP circuit and a viable target for specific ANP augmentation.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Karbalaei Sadegh, MardjanehLund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,WCMM- Wallenberg center för molekylär medicinsk forskning,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,WCMM-Wallenberg Centre for Molecular Medicine(Swepub:lu)med-mkb
(författare)
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Morley, MichaelUniversity of Pennsylvania
(författare)
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Roselli, CarolinaBroad Institute
(författare)
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Ellinor, Patrick TBroad Institute,Massachusetts General Hospital
(författare)
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Cappola, Thomas PUniversity of Pennsylvania
(författare)
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Smith, J. GustavLund University,Lunds universitet,Heart Failure and Mechanical Support,Forskargrupper vid Lunds universitet,Molecular Epidemiology and Cardiology,Cardiovascular Epigenetics,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Broad Institute,Skåne University Hospital(Swepub:lu)med-gvs
(författare)
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Gidlöf, OlofLund University,Lunds universitet,Molekylär kardiologi,Forskargrupper vid Lunds universitet,Molecular Epidemiology and Cardiology,Cardiovascular Epigenetics,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Molecular Cardiology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine(Swepub:lu)med-ogf
(författare)
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Molecular Epidemiology and CardiologyForskargrupper vid Lunds universitet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:JCI Insight: American Society for Clinical Investigation4:192379-3708
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