Inhibition of microRNA-33b specifically ameliorates abdominal aortic aneurysm formation via suppression of inflammatory pathways View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-07-14

AUTHORS

Tomohiro Yamasaki, Takahiro Horie, Satoshi Koyama, Tetsushi Nakao, Osamu Baba, Masahiro Kimura, Naoya Sowa, Kazuhisa Sakamoto, Kazuhiro Yamazaki, Satoshi Obika, Yuuya Kasahara, Jun Kotera, Kozo Oka, Ryo Fujita, Takashi Sasaki, Akihiro Takemiya, Koji Hasegawa, Kenji Minatoya, Takeshi Kimura, Koh Ono

ABSTRACT

Abdominal aortic aneurysm (AAA) is a lethal disease, but no beneficial therapeutic agents have been established to date. Previously, we found that AAA formation is suppressed in microRNA (miR)-33-deficient mice compared with wild-type mice. Mice have only one miR-33, but humans have two miR-33 s, miR-33a and miR-33b. The data so far strongly support that inhibiting miR-33a or miR-33b will be a new strategy to treat AAA. We produced two specific anti-microRNA oligonucleotides (AMOs) that may inhibit miR-33a and miR-33b, respectively. In vitro studies showed that the AMO against miR-33b was more effective; therefore, we examined the in vivo effects of this AMO in a calcium chloride (CaCl2)-induced AAA model in humanized miR-33b knock-in mice. In this model, AAA was clearly improved by application of anti-miR-33b. To further elucidate the mechanism, we evaluated AAA 1 week after CaCl2 administration to examine the effect of anti-miR-33b. Histological examination revealed that the number of MMP-9-positive macrophages and the level of MCP-1 in the aorta of mice treated with anti-miR-33b was significantly reduced, and the serum lipid profile was improved compared with mice treated with control oligonucleotides. These results support that inhibition of miR-33b is effective in the treatment for AAA. More... »

PAGES

11984

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-022-16017-5

DOI

http://dx.doi.org/10.1038/s41598-022-16017-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1149463960

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35835906


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335 grid-institutes:grid.418306.8 schema:alternateName Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Shonan Health Innovation Park, 2-26-1, Muraoka-Higashi, Fujisawa-shi, 251-8555, Kanagawa, Japan
336 schema:name Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Shonan Health Innovation Park, 2-26-1, Muraoka-Higashi, Fujisawa-shi, 251-8555, Kanagawa, Japan
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338 grid-institutes:grid.482562.f schema:alternateName Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki-shi, 567-0085, Osaka, Japan
339 schema:name Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki-shi, 567-0085, Osaka, Japan
340 Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita-shi, 565-0871, Osaka, Japan
341 rdf:type schema:Organization
 




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