Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways

Nakao, Tetsushi; Horie, Takahiro; Baba, Osamu; Nishiga, Masataka; Nishino, Tomohiro; Izuhara, Masayasu; Kuwabara, Yasuhide; Nishi, Hitoo; Usami, Shunsuke; Nakazeki, Fumiko; Ide, Yuya; Koyama, Satoshi; Kimura, Masahiro; Sowa, Naoya; Ohno, Satoko; Aoki, Hiroki; Hasegawa, Koji; Sakamoto, Kazuhisa; Minatoya, Kenji; Kimura, Takeshi; Ono, Koh

doi:10.1161/atvbaha.117.309768

Cited by 74 publications

(60 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Supporting this result, gene expression analysis confirmed no significant difference in the expression of Abca1 or Abcg1 in macrophages obtained from miR-33 KOKI mice compared with miR-33 WT mice ( Figure 6B and 6C). Although previous reports also suggested the participation of miR-33 in macrophage inflammatory phenotypes, 15,16 inflammatory gene expression patterns were similar between macrophages obtained from miR-33 KOKI mice compared with miR-33 WT mice ( Figure 6D).…”

Section: Relevant Functions Of Mir-33a and Mir-33b In Macrophagessupporting

confidence: 54%

“…Notably, we and other groups have shown previously that miR-33 potentially affects many biological pathways, including cholesterol homeostasis. [8][9][10][11][12][13][14][15][16][17][18] In vivo deletion or inhibition of miR-33 using antisense oligonucleotide improved the serum cholesterol profile and enhanced cholesterol reverse transport of not only mice, but also nonhuman primates. These favorable changes in serum cholesterol profile or cholesterol reverse transport reduced atherosclerotic plaque progression in mice.…”

mentioning

confidence: 99%

See 1 more Smart Citation

260Identification of differential roles of microRNA-33a and -33b during atherosclerosis progression with genetically modified mice

Horie

Koyama

Kimura

et al. 2019

European Heart Journal

View full text Add to dashboard Cite

Background MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, indicated that miR-33a located within the intron of sterol regulatory element-binding factor (SREBF) 2 targets cholesterol transporter ATP-binding cassette protein A1 (ABCA1) or other anti-atherogenic targets and contributes to atherogenesis. Its inhibition or deletion is known to result in the amelioration of atherosclerosis. However, mice lack the other member of miR-33 family, miR-33b, which exists in humans. Precise evaluation and comparison of the responsibilities of these two miRs during the progression of atherosclerosis are essential and need to be investigated. Methods and results The difference between miR-33a and miR-33b in vitro and in vivo were analyzed from multiple directions using genetically modified miR-33a knock-out (KO) and miR-33b knock-in (KI) humanized mice. At first, we performed transcriptomic analysis of primary cultured hepatocytes transfected with synthetic miR-33a, miR-33b, and a control miR and found similar potential target repression and targeting motif of miR-33a and miR-33b in vitro. However, we noticed distinct expression patterns of miR-33a and miR-33b in several organs. By crossing miR-33a KO and miR-33b KI mice, we established four strains with or without miR-33a and miR-33b. Comparison of these strains showed distinct distribution and regulation of miR-33 family. In particular, comparison between mice with only miR-33a (wild-type mice) and mice with only miR-33b (miR-33a−/− miR-33b+/+) revealed 4-fold predominant expression of miR-33b in the liver. Such differential expression resulted in a reduced expression of target genes such as ABCA1 and worsened serum cholesterol profile in mice with only miR-33b. On the contrary, in macrophages the expression levels of miR-33 family genes were similar and their effects on target genes and cholesterol efflux capacity to ApoA-I or HDL cholesterol (HDL-C) were almost comparable. To evaluate the whole body atherogenic potency, we developed ApoE−/− miR-33a+/+ miR-33b−/− mice and ApoE−/− miR-33a−/− miR-33b+/+ mice. ApoE−/− miR-33a−/− miR-33b+/+ mice developed increased atherosclerotic plaque compared with ApoE−/− miR-33a+/+ miR-33b−/− mice, in line with the predominant expression of miR-33b in the liver and decreased serum HDL-C levels whose lower cholesterol efflux capacity were confirmed in 3H-labeled macrophages. On the contrary, a bone marrow transplantation study showed no significant difference in atherosclerosis and serum cholesterol profile, and this was consistent with the relevant expression levels of miR-33a and miR-33b in bone marrow cells. Conclusions miR-33 family exhibited differences in distribution and regulation, and particularly in the progression of atherosclerosis, miR-33b would be more potent than miR-33a.

show abstract

Section: Relevant Functions Of Mir-33a and Mir-33b In Macrophagessupporting

confidence: 54%

mentioning

confidence: 99%

260Identification of differential roles of microRNA-33a and -33b during atherosclerosis progression with genetically modified mice

Horie

Koyama

Kimura

et al. 2019

European Heart Journal

View full text Add to dashboard Cite

show abstract

“…Further, pre-miR-24, anti-miR-29b and anti-miR-33 treatment can attenuate aneurysm in mouse models. 187,192,194 These results strongly reveal that miRNA treatment may be a novel and useful therapeutic strategy for AA.…”

Section: Aneurysmmentioning

confidence: 78%

The regulatory role of microRNAs in angiogenesis‐related diseases

Sun

Lei

et al. 2018

J Cellular Molecular Medi

116

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression at a post‐transcriptional level via either the degradation or translational repression of a target mRNA. They play an irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis‐related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA‐based biomarkers in the diagnosis, treatment and prognosis of angiogenesis‐related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.

show abstract

“…It is important to note that in this work, the presence of circulating levels of miR-33a is further characterized, 10 times higher than the levels of miR33b. In the context of IR overlapping with ageing, the circulating levels of the miR-33 family presented in this study have not been previously reported; in this regard, there are two scenarios that we be able to distinguish: first, the reports that precede this study are related to miR-33 intracellular expression (endogenous) or circulating levels in other diseases, 37,38 while in this study we focused on mature (circulating levels) miR-33 in individuals with the novo IR classification, and second, the individuals included in this study were characterized with IR according to a strict system, the Stern criteria; 15 in this sense, we cannot establish controversy with others studies.…”

Section: Discussionmentioning

confidence: 67%

Ageing influences the relationship of circulating miR-33a and miR-33b levels with insulin resistance and adiposity

Corona-Meraz

Mercado

Ortega

et al. 2018

Diabetes and Vascular Disease Research

View full text Add to dashboard Cite

Objective: The identification of circulating microRNAs related to abnormal metabolic function may be useful in the context of ageing, adiposity and insulin resistance. The miR-33a/b has been shown to control the expression of genes involved in fatty acid biosynthesis, impaired metabolism and insulin resistance. In this study, we aimed to identify differences in circulating miR-33a/b levels according to age-related metabolic impairment and increased adiposity. Methods: This study included 80 individuals (30.2% with obesity, 70% females) classified according to insulin resistance (Stern's criteria) and age [young (20-39 years) and senior (40-59 years)]. Body fat was evaluated using bioelectrical impedance, biochemical markers by colorimetric, enzymatic and immuno-turbidimetry methods. TaqMan measures of circulating miR-33a and miR-33b with quantitative reverse transcription polymerase chain reaction in serum were assessed in association with clinical outputs. Results: Circulating miR-33a and miR-33b levels showed significant association with fatness, the lipid profile and biomarkers of impaired glucose metabolism. Both miR-33a and miR-33b were associated with visceral adiposity index in non-insulin resistance and insulin resistance individuals. More important, for miR-33a circulating levels in senior group, receiver operating characteristic curve analyses showed area under the curve 0.804 (p = 0.010; 95% confidence interval = 0.655-0.952). Conclusion: Ageing influenced the relationship of circulating miR-33a and miR-33b with insulin resistance and increased adiposity.

show abstract

Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways

Abstract: These data strongly suggest that inhibition of miR-33 will be effective as a novel strategy for treating AAA.

Cited by 74 publications

References 38 publications

260Identification of differential roles of microRNA-33a and -33b during atherosclerosis progression with genetically modified mice

260Identification of differential roles of microRNA-33a and -33b during atherosclerosis progression with genetically modified mice

The regulatory role of microRNAs in angiogenesis‐related diseases

Ageing influences the relationship of circulating miR-33a and miR-33b levels with insulin resistance and adiposity

Contact Info

Product

Resources

About