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Cited by 13Aortic aneurysm repair treatmentsMicroRNA in disease regulationConnective tissue disorders research

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

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Yamasaki, Tomohiro, Horie, Takahiro, Koyama, Satoshi, Nakao, Tetsushi, Baba, Osamu, Kimura, Masahiro, Sowa, Naoya, Sakamoto, Kazuhisa +12 more·2022·Scientific Reports
DOI 10.1038/s41598-022-16017-5PMC PMC9283493
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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 (CaCl 2)-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 CaCl 2 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.

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Cited by

Sorted by citations

Authors
Yamasaki, T., Horie, T., Koyama, S., Nakao, T., Baba, O., Kimura, M., Sowa, N., Sakamoto, K., Yamazaki, K., Obika, S., Kasahara, Y., Kotera, J., Oka, K., Fujita, R., Sasaki, T., Takemiya, A., Hasegawa, K., Minatoya, K., Kimura, T., & Ono, K.
Affiliations
  • Kyoto University (JP)
  • Kyoto Medical Center (JP)
  • National Institute of Biomedical Innovation, Health and Nutrition (JP)
  • Tanabe Pharma Corporation (Japan) (JP)
Corresponding author
  • Horie, Takahiro
  • Ono, Koh
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2022-07-14
Volume
12
Issue
1
Pages
11984-11984
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-022-16017-5
PMC
PMC9283493
OpenAlex
W4285389298
Cited by
13
References
6
Citations by year
2026: 2 · 2025: 6 · 2024: 3 · 2023: 2
FWCI
1.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
Funders
  • Mochida Memorial Foundation for Medical and Pharmaceutical Research
  • Suzuken Memorial Foundation
  • Bristol Myers Squibb
  • Fujiwara Memorial Foundation
  • Japan Society for the Promotion of Science (17K09860 and 20K08904, 1605297, 17H04177, 17H05599, 20H03675, 17H04177, 17H05599, and 20H03675)
  • The Vehicle Racing Commemorative Foundation
  • Japan Agency for Medical Research and Development (JP19fk0210112, 21ym0126013h0001, 22ym0126074h0001)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Aortic aneurysm repair treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
Keywords
abdominal aortic aneurysm, miR-33a, anti-miR oligonucleotides, microRNA inhibition, inflammation, MMP-9, macrophages, MCP-1, lipid profile
MeSH terms
Antagomirs, Animals, Aorta, Abdominal, Calcium Chloride, Disease Models, Animal, Humans, Mice, Inbred C57BL, Aortic Aneurysm, Abdominal, MicroRNAs, Mice

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