Researchers showed that KPT-330 prevented, attenuated and mitigated calcific nodule formation in heart valve interstitial cells in vitro, and prevented calcific aortic valve disease in Klotho-/- mice.
[Circulation Research]
1254621
{1254621:I4IHX83M}
apa
50
1
159413
https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-e647db6ffd5fe20cf8d228fb681eb4ce%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22I4IHX83M%22%2C%22library%22%3A%7B%22id%22%3A1254621%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Dutta%20Punashi%20et%20al.%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EDutta%20Punashi%2C%20Kodigepalli%20Madhav%20Karthik%2C%20LaHaye%20Stephanie%2C%20Thompson%20J%20Will%2C%20Rains%20Sarah%2C%20Nagel%20Casey%2C%20Thatcher%20Kaitlyn%2C%20Hinton%20Robert%20B%2C%20%26amp%3B%20Lincoln%20Joy.%20%28n.d.%29.%20KPT-330%20Prevents%20Aortic%20Valve%20Calcification%20via%20a%20Novel%20C%5C%2FEBP%26%23x3B2%3B%20Signaling%20Pathway.%20%3Ci%3ECirculation%20Research%3C%5C%2Fi%3E%2C%20%3Ci%3E0%3C%5C%2Fi%3E%280%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1161%5C%2FCIRCRESAHA.120.318503%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1161%5C%2FCIRCRESAHA.120.318503%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D1254621%26amp%3Bitem_key%3DI4IHX83M%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22KPT-330%20Prevents%20Aortic%20Valve%20Calcification%20via%20a%20Novel%20C%5C%2FEBP%5Cu03b2%20Signaling%20Pathway%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Dutta%20Punashi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Kodigepalli%20Madhav%20Karthik%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22LaHaye%20Stephanie%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Thompson%20J%20Will%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Rains%20Sarah%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Nagel%20Casey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Thatcher%20Kaitlyn%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Hinton%20Robert%20B%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22name%22%3A%22Lincoln%20Joy%22%7D%5D%2C%22abstractNote%22%3A%22Rationale%3A%20Calcific%20Aortic%20Valve%20Disease%20%28CAVD%29%20affects%20more%20than%205.2%20million%20people%20in%20the%20US.%20The%20only%20effective%20treatment%20is%20surgery%20and%20this%20comes%20with%20complications%20and%20no%20guarantee%20of%20long-term%20success.%20Objective%3A%20Outcomes%20from%20pharmacological%20initiatives%20remain%20unsubstantiated%20and%20therefore%20the%20aim%20of%20this%20study%20is%20to%20determine%20if%20repurposing%20a%20selective%20XPO1%20inhibitor%20drug%20%28KPT-330%29%20is%20beneficial%20in%20the%20treatment%20of%20CAVD.%20Methods%20and%20Results%3A%20We%20show%20that%20KPT-330%20prevents%2C%20attenuates%20and%20mitigates%20calcific%20nodule%20formation%20in%20heart%20valve%20interstitial%20cells%20%28VICs%29%20in%20vitro%2C%20and%20prevents%20CAVD%20in%20Klotho-%5C%2F-%20mice.%20Using%20RNA-sequencing%20and%20Mass%20Spectrometry%20we%20show%20that%20KPT-330%27s%20beneficial%20effect%20is%20mediated%20by%20inhibiting%20nuclear%20export%20of%20the%20transcription%20factor%20C%5C%2FEBP%5Cu03b2%20in%20VICs%2C%20leading%20to%20repression%20of%20canonical%20Wnt%20signaling%2C%20in%20part%20through%20activation%20of%20the%20Wnt%20antagonist%20Axin1%2C%20and%20a%20subsequent%20decrease%20in%20pro-osteogenic%20markers%20and%20cell%20viability.%20Conclusions%3A%20Our%20findings%20have%20met%20a%20critical%20need%20to%20discover%20alterative%2C%20pharmacological-based%20therapies%20in%20the%20treatment%20of%20CAVD.%22%2C%22date%22%3A%22%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1161%5C%2FCIRCRESAHA.120.318503%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.ahajournals.org%5C%2Fdoi%5C%2F10.1161%5C%2FCIRCRESAHA.120.318503%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-02-24T22%3A07%3A35Z%22%7D%7D%5D%7D
Dutta Punashi, Kodigepalli Madhav Karthik, LaHaye Stephanie, Thompson J Will, Rains Sarah, Nagel Casey, Thatcher Kaitlyn, Hinton Robert B, & Lincoln Joy. (n.d.). KPT-330 Prevents Aortic Valve Calcification via a Novel C/EBPβ Signaling Pathway. Circulation Research, 0(0). https://doi.org/10.1161/CIRCRESAHA.120.318503 Cite
