Sökning: onr:"swepub:oai:openarchive.ki.se:10616/48166" > Phospholamban antis...
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000 | 04368naa a2200745 4500 | |
001 | oai:openarchive.ki.se:10616/48166 | |
003 | SwePub | |
008 | 240410s2021 | |||||||||||000 ||eng| | |
009 | oai:gup.ub.gu.se/310644 | |
009 | oai:prod.swepub.kib.ki.se:148482339 | |
022 | a 2041-1723 | |
024 | 7 | a 10616/481662 hdl |
024 | 7 | a http://hdl.handle.net/10616/481662 URI |
024 | 7 | a https://doi.org/10.1038/s41467-021-25439-02 DOI |
024 | 7 | a https://gup.ub.gu.se/publication/3106442 URI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1484823392 URI |
040 | a (SwePub)kid (SwePub)gu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Beverborg, Niels Grote4 aut |
245 | 1 0 | a Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy |
264 | c 2021-08-30 | |
264 | 1 | a Stockholm :b Karolinska Institutet, Dept of Cell and Molecular Biology,c 2021 |
338 | a electronic2 rdacarrier | |
520 | a Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca2+ handling is a key feature of HF pathophysiology. Restoring the Ca2+ regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp−/−), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng |
700 | 1 | a Spater, Daniela4 aut |
700 | 1 | a Knoll, Ralphu Karolinska Institutet4 aut |
700 | 1 | a Hidalgo, Alejandro4 aut |
700 | 1 | a Yeh, Steve T4 aut |
700 | 1 | a Elbeck, Zaher4 aut |
700 | 1 | a Sillje, Herman H W4 aut |
700 | 1 | a Eijgenraam, Tim R4 aut |
700 | 1 | a Siga, Humam4 aut |
700 | 1 | a Zurek, Magdalena4 aut |
700 | 1 | a Palmér, Malinu Gothenburg University,Göteborgs universitet,Core Facilities, Experimentell Biomedicin,Core Facilities, Experimental Biomedicine4 aut0 (Swepub:gu)xpamal |
700 | 1 | a Pehrsson, Susanne4 aut |
700 | 1 | a Albery, Tamsin4 aut |
700 | 1 | a Bomer, Nils4 aut |
700 | 1 | a Hoes, Martijn F4 aut |
700 | 1 | a Boogerd, Cornelis J4 aut |
700 | 1 | a Frisk, Michael4 aut |
700 | 1 | a van Rooij, Eva4 aut |
700 | 1 | a Damle, Sagar4 aut |
700 | 1 | a Louch, William E4 aut |
700 | 1 | a Wang, Qing-Dong4 aut |
700 | 1 | a Fritsche-Danielson, Regina4 aut |
700 | 1 | a Chien, Kenneth R4 aut |
700 | 1 | a Hansson, Kenny M4 aut |
700 | 1 | a Mullick, Adam E4 aut |
700 | 1 | a de Boer, Rudolf A4 aut |
700 | 1 | a van der Meer, Peter4 aut |
710 | 2 | a Karolinska Institutetb Core Facilities, Experimentell Biomedicin4 org |
710 | 2 | a Karolinska Institutet |
710 | 2 | a Karolinska Institutet |
773 | 0 | t Nature Communicationsd Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biologyx 2041-1723 |
856 | 4 | u http://hdl.handle.net/10616/48166x primaryx Object in contextx freey FULLTEXT |
856 | 4 | u https://www.nature.com/articles/s41467-021-25439-0.pdf |
856 | 4 8 | u http://hdl.handle.net/10616/48166 |
856 | 4 8 | u https://doi.org/10.1038/s41467-021-25439-0 |
856 | 4 8 | u https://gup.ub.gu.se/publication/310644 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:148482339 |
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