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Anti-miR-33 Therapy Does Not Alter the Progression of Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
Open accessAbstract
Objective—: To determine the efficacy of long-term anti-miR-33 therapy on the progression of atherosclerosis in high-fat, high-cholesterol–fed Ldlr –/– mice. Methods and Results—: Ldlr –/– mice received saline, or control or anti-miR-33 oligonucleotides once a week for 14 weeks. The treatment was effective, as measured by reduced levels of hepatic miR-33 and increased hepatic expression of miR-33 targets. Analysis of plasma samples revealed an initial elevation in high-density lipoprotein cholesterol after 2 weeks of treatment that was not sustained by the end of the experiment. Additionally, we found a significant increase in circulating triglycerides in anti-miR-33–treated mice, compared with controls. Finally, examination of atheromata revealed no significant changes in the size or composition of lesions between the 3 groups. Conclusion—: Prolonged silencing of miR-33 fails to maintain elevated plasma high-density lipoprotein cholesterol and does not prevent the progression of atherosclerosis in Ldlr –/– mice.
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“However, other similar studies did not observe any beneficial effects of anti-miR-33 therapy on atherogenesis (Marquart et al., 2013).”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Marquart et al., 2013
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“Another study did not find reduced aortic lesions in anti-miR-33 treated mice (Marquart et al., 2013).”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Marquart et al., 2013
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MiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner, K. J., Suárez, Y., Dávalos, A., Parathath, S., Fitzgerald, M. L., Tamehiro, N., Fisher, E. A., Moore, K. J., & Fernández-Hernando, C. (2010) · Science · doi:10.1126/science.1189862 · Cited by 1,260
MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
Najafi-Shoushtari, S. H., Kristo, F., Li, Y., Shioda, T., Cohen, D. E., Gerszten, R. E., & Näär, A. M. (2010) · Science · doi:10.1126/science.1189123 · Cited by 957
Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides
Rayner, K. J., Esau, C. C., Hussain, F. N., McDaniel, A. L., Marshall, S. M., van Gils, J. M., Ray, T. D., Sheedy, F. J., Goedeke, L., Liu, X., et al. (2011) · Nature · doi:10.1038/nature10486 · Cited by 706
Rayner, K. J., Sheedy, F. J., Esau, C. C., Hussain, F. N., Temel, R. E., Parathath, S., van Gils, J. M., Rayner, A. J., Chang, A. N., Suarez, Y., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57275 · Cited by 690 · cited 3×
“increase HDL-c and accelerate the regression of atherosclerotic lesions in hyperlipidemic Ldlr mice switched to standard chow diet.(7) However, no reports are yet available”
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos, A., Goedeke, L., Smibert, P., Ramírez, C. M., Warrier, N. P., Andreo, U., Cirera-Salinas, D., Rayner, K., Suresh, U., Pastor-Pareja, J. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102281108 · Cited by 670
miR-33 links SREBP-2 induction to repression of sterol transporters
Marquart, T. J., Allen, R. M., Ory, D. S., & Baldán, Á. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005191107 · Cited by 562
Self-citationHorie, T., Ono, K., Horiguchi, M., Nishi, H., Nakamura, T., Nagao, K., Kinoshita, M., Kuwabara, Y., Marusawa, H., Iwanaga, Y., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008499107 · Cited by 384
Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation*
Gerin, I., Clerbaux, L.-A., Haumont, O., Lanthier, N., Das, A. K., Burant, C. F., Leclercq, I. A., MacDougald, O. A., & Bommer, G. T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152090 · Cited by 382
Is it time to revise the HDL cholesterol hypothesis?
Rader, D. J., & Tall, A. R. (2012) · Nature Medicine · doi:10.1038/nm.2937 · Cited by 279
MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE −/− Mice
Horie, T., Baba, O., Kuwabara, Y., Chujo, Y., Watanabe, S., Kinoshita, M., Horiguchi, M., Nakamura, T., Chonabayashi, K., Hishizawa, M., et al. (2012) · Journal of the American Heart Association · doi:10.1161/jaha.112.003376 · Cited by 220
Cited by
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MicroRNA Regulation of Atherosclerosis
Feinberg, M. W., & Moore, K. J. (2016) · Circulation Research · doi:10.1161/circresaha.115.306300 · Cited by 638
Development of microRNA therapeutics is coming of age
van Rooij, E., & Kauppinen, S. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201100899 · Cited by 625
Ouimet, M., Ediriweera, H. N., Gundra, U. M., Sheedy, F. J., Ramkhelawon, B., Hutchison, S. B., Rinehold, K., van Solingen, C., Fullerton, M. D., Cecchini, K., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81676 · Cited by 394
Transcriptional Control of Hepatic Lipid Metabolism by SREBP and ChREBP
Xu, X., So, J., Park, J., & Lee, A. (2013) · Seminars in Liver Disease · doi:10.1055/s-0033-1358523 · Cited by 321
Role of Flow-Sensitive microRNAs in Endothelial Dysfunction and Atherosclerosis
Kumar, S., Kim, C. W., Simmons, R. D., & Jo, H. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303425 · Cited by 274
Metadata
- Authors
- Marquart, T. J., Wu, J., Lusis, A. J., & Baldán, Á.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2013-03
- Volume
- 33
- Issue
- 3
- Pages
- 455-458
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC3587119
- OpenAlex
- W2169384530
- Cited by
- 110
- References
- 14
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 14 · 2016: 18 · 2015: 15 · 2014: 18 · 2013: 16
- FWCI
- 22.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Saint Louis University
- National Heart, Lung, and Blood Institute (HL030568, HL095154, P01HL030568, R01HL095154, HL107794, R01HL107794)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- miR-33, atherosclerosis progression, LDL receptor-deficient mice, HDL cholesterol, high-fat high-cholesterol diet, microRNA silencing
- MeSH terms
- Animals, Aorta, Aortic Diseases, Cholesterol, Dietary, Disease Models, Animal, Cholesterol, HDL, Liver, Male, Receptors, LDL, Time Factors, Triglycerides, Biomarkers, Down-Regulation, Oligonucleotides, Antisense, Mice, Knockout, Disease Progression, MicroRNAs, Atherosclerosis, Mice
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