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Cited by 23Cholesterol and Lipid MetabolismMicroRNA in disease regulationAtherosclerosis and Cardiovascular Diseases

Identification of Differential Roles of MicroRNA‐33a and ‐33b During Atherosclerosis Progression With Genetically Modified Mice

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Koyama, Satoshi, Horie, Takahiro, Nishino, Tomohiro, Baba, Osamu, Sowa, Naoya, Miyasaka, Yui, Kuwabara, Yasuhide, Nakao, Tetsushi +16 more·2019·Journal of the American Heart Association
DOI 10.1161/jaha.119.012609PMC PMC6662357
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Abstract

Background: Micro RNA (miR)‐33 targets cholesterol transporter ATP ‐binding cassette protein A1 and other antiatherogenic targets and contributes to atherogenic progression. Its inhibition or deletion is known to result in the amelioration of atherosclerosis in mice. However, mice lack the other member of the miR‐33 family, miR‐33b, which exists in humans and other large mammals. Thus, precise evaluation and comparison of the responsibilities of these 2 miRs during the progression of atherosclerosis has not been reported, although they are essential. Methods and Results: In this study, we performed a comprehensive analysis of the difference between the function of miR‐33a and miR‐33b using genetically modified mice. We generated 4 strains with or without miR‐33a and miR‐33b. Comparison between mice with only miR‐33a (wild‐type mice) and mice with only miR‐33b (miR‐33a −/− /miR‐33b +/+ ) revealed the dominant expression of miR‐33b in the liver. To evaluate the whole body atherogenic potency of miR‐33a and miR‐33b, we developed apolipoprotein E–deficient/miR‐33a +/+ /miR‐33b −/− mice and apolipoprotein E–deficient/miR‐33a −/− /miR‐33b +/+ mice. With a high‐fat and high‐cholesterol diet, the apolipoprotein E–deficient/miR‐33a −/− /miR‐33b +/+ mice developed increased atherosclerotic plaque versus apolipoprotein E–deficient/miR‐33a +/+ /miR‐33b −/− mice, in line with the predominant expression of miR‐33b in the liver and worsened serum cholesterol profile. By contrast, a bone marrow transplantation study showed no significant difference, which was consistent with the relevant expression levels of miR‐33a and miR‐33b in bone marrow cells. Conclusions: The miR‐33 family exhibits differences in distribution and regulation and particularly in the progression of atherosclerosis; miR‐33b would be more potent than miR‐33a.

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Authors
Koyama, S., Horie, T., Nishino, T., Baba, O., Sowa, N., Miyasaka, Y., Kuwabara, Y., Nakao, T., Nishiga, M., Nishi, H., Nakashima, Y., Nakazeki, F., Ide, Y., Kimura, M., Tsuji, S., Ruiz Rodriguez, R., Xu, S., Yamasaki, T., Otani, C., Watanabe, T., Nakamura, T., Hasegawa, K., Kimura, T., & Ono, K.
Affiliations
  • Kyoto University (JP)
  • Department of Cardiovascular Medicine Graduate School of Medicine Kyoto University Kyoto Japan
  • Kansai Medical University (JP)
  • Kyoto Medical Center (JP)
Corresponding author
  • Horie, Takahiro
  • Ono, Koh
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-07-02
Volume
8
Issue
13
Pages
e012609-e012609
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.119.012609
PMC
PMC6662357
OpenAlex
W2954469793
Cited by
23
References
11
Citations by year
2025: 4 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 8 · 2020: 1 · 2019: 1
FWCI
2.86
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
Funders
Japan Society for the Promotion of Science (17H04177)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
atherosclerosis progression, ABCA1, ApoE-deficient mice, high-fat high-cholesterol diet, serum cholesterol, liver expression, bone marrow transplantation, genetically modified mice, atherosclerotic plaque
MeSH terms
Mice, Knockout, ApoE, Animals, Apolipoproteins B, Cholesterol, Cholesterol, Dietary, Liver, Mice, Transgenic, Triglycerides, Bone Marrow Transplantation, Macrophages, Peritoneal, Mice, Knockout, Disease Progression, Gene Expression Profiling, Hepatocytes, MicroRNAs, Atherosclerosis, Mice, Gene Knock-In Techniques, Plaque, Atherosclerotic, Diet, High-Fat

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