CoChat
Sign Up
Cited by 89Cholesterol and Lipid MetabolismMicroRNA in disease regulationLipoproteins and Cardiovascular Health

MicroRNA Modulation of Cholesterol Homeostasis

Open access
Fernández-Hernando, Carlos, Moore, Kathryn J.·2011·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/atvbaha.111.226688PMC PMC3298754
Open this paper in CoChat — free account

Abstract

Although the roles of the sterol response element binding protein-1 (SREBP1) and SREBP2 transcription factors in regulating fatty acid and cholesterol synthesis and uptake have been known for some time, it was recently discovered that 2 related microRNAs (miRs), miR-33a and miR-33b , are embedded in these genes. Studies indicate that miR-33a and miR-33b act with their host genes, Srebp2 and Srebp1 , respectively, to reciprocally regulate cholesterol homeostasis and fatty acid metabolism in a negative feedback loop. miR-33 has been shown to posttranscriptionally repress key genes involved in cellular cholesterol export and high-density lipoprotein metabolism ( Abca1 , Abcg1 , Npc1 ), fatty acid oxidation ( Crot , Cpt1a , Hadhb , Ampk ), and glucose metabolism ( Sirt6 , Irs2 ). Delivery of inhibitors of miR-33 in vitro and in vivo relieves repression of these genes, resulting in upregulation of the associated metabolic pathways. In mouse models, miR-33 antagonism has proven to be an effective strategy for increasing plasma high-density lipoprotein cholesterol and fatty acid oxidation and protecting from atherosclerosis. These exciting findings have opened up promising new avenues for the development of therapeutics to treat dyslipidemia and other metabolic disorders.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/atvbaha.111.226688

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 32

  1. [1]Ambros V MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing Cell 2003 113 673 676 12809598
  2. [2]Ambros V The functions of animal microRNAs Nature 2004 431 350 355 15372042
  3. [3]Bartel DP MicroRNAs: target recognition and regulatory functions Cell 2009 136 215 233 19167326 PMC3794896
  4. [4]Filipowicz W Bhattacharyya SN Sonenberg N Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008 9 102 114 18197166
  5. [5]Lee RC Feinbaum RL Ambros V The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 Cell 1993 75 843 854 8252621
  6. [7]Marquart TJ Allen RM Ory DS Baldan A miR-33 links SREBP-2 induction to repression of sterol transporters Proc Natl Acad Sci U S A 2010 107 12228 12232 20566875 PMC2901433
  7. [9]Rayner KJ Suarez Y Davalos A Parathath S Fitzgerald ML Tamehiro N Fisher EA Moore KJ Fernandez-Hernando C MiR-33 contributes to the regulation of cholesterol homeostasis Science 2010 328 1570 1573 20466885 PMC3114628
  8. [10]Brown MS Goldstein JL The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor Cell 1997 89 331 340 9150132
  9. [11]Horton JD Sterol regulatory element-binding proteins: transcriptional activators of lipid synthesis Biochem Soc Trans 2002 30 1091 1095 12440980
  10. [12]Osborne TF Sterol regulatory element-binding proteins (SREBPs): key regulators of nutritional homeostasis and insulin action J Biol Chem 2000 275 32379 32382 10934219
  11. [15]Horie T Ono K Horiguchi M Nishi H Nakamura T Nagao K Kinoshita M Kuwabara Y Marusawa H Iwanaga Y Hasegawa K Yokode M Kimura T Kita T MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo Proc Natl Acad Sci U S A 2010 107 17321 17326 20855588 PMC2951399
  12. [17]Tall AR Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins J Intern Med 2008 263 256 273 18271871
  13. [18]Tall AR Yvan-Charvet L Terasaka N Pagler T Wang N HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis Cell Metab 2008 7 365 375 18460328
  14. [19]Oram JF Tangier disease and ABCA1 Biochim Biophys Acta 2000 1529 321 330 11111099
  15. [20]Oram JF Yokoyama S Apolipoprotein-mediated removal of cellular cholesterol and phospholipids J Lipid Res 1996 37 2473 2491 9017501
  16. [22]Kim HS Xiao C Wang RH Lahusen T Xu X Vassilopoulos A Vazquez-Ortiz G Jeong WI Park O Ki SH Gao B Deng CX Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis Cell Metab 2010 12 224 236 20816089 PMC2935915
  17. [23]Herrera-Merchan A Cerrato C Luengo G Dominguez O Piris MA Serrano M Gonzalez S miR-33-mediated downregulation of p53 controls hematopoietic stem cell self-renewal Cell Cycle 2010 9 3277 3285 20703086
  18. [24]Bengoechea-Alonso MT Ericsson J Cdk1/cyclin B-mediated phosphorylation stabilizes SREBP1 during mitosis Cell Cycle 2006 5 1708 1718 16880739
  19. [25]Bengoechea-Alonso MT Punga T Ericsson J Hyperphosphorylation regulates the activity of SREBP1 during mitosis Proc Natl Acad Sci U S A 2005 102 11681 11686 16081540 PMC1187962
  20. [26]Fernandez C Lobo Md Mdel V Gomez-Coronado D Lasuncion MA Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation Exp Cell Res 2004 300 109 120 15383319
  21. [27]Martinez-Botas J Suarez Y Ferruelo AJ Gomez-Coronado D Lasuncion MA Cholesterol starvation decreases p34(cdc2) kinase activity and arrests the cell cycle at G2 FASEB J 1999 13 1359 1370 10428760
  22. [28]Ibrahim AF Weirauch U Thomas M Grunweller A Hartmann RK Aigner A MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma Cancer Res 2011 71 5214 5224 21690566
  23. [30]Choudhury RP Rong JX Trogan E Elmalem VI Dansky HM Breslow JL Witztum JL Fallon JT Fisher EA High-density lipoproteins retard the progression of atherosclerosis and favorably remodel lesions without suppressing indices of inflammation or oxidation Arterioscler Thromb Vasc Biol 2004 24 1904 1909 15319266
  24. [31]Paszty C Maeda N Verstuyft J Rubin EM Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice J Clin Invest 1994 94 899 903 8040345 PMC296173
  25. [32]Plump AS Scott CJ Breslow JL Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse Proc Natl Acad Sci U S A 1994 91 9607 9611 7937814 PMC44862
  26. [33]Rubin EM Krauss RM Spangler EA Verstuyft JG Clift SM Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI Nature 1991 353 265 267 1910153
  27. [34]Feig JE Rong JX Shamir R Sanson M Vengrenyuk Y Liu J Rayner K Moore K Garabedian M Fisher EA HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells Proc Natl Acad Sci U S A 108 7166 7171 21482781 PMC3084076
  28. [35]Rong JX Li J Reis ED Choudhury RP Dansky HM Elmalem VI Fallon JT Breslow JL Fisher EA Elevating high-density lipoprotein cholesterol in apolipoprotein E-deficient mice remodels advanced atherosclerotic lesions by decreasing macrophage and increasing smooth muscle cell content Circulation 2001 104 2447 2452 11705823
  29. [36]Tangirala RK Tsukamoto K Chun SH Usher D Pure E Rader DJ Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice Circulation 1999 100 1816 1822 10534470
  30. [37]Badimon JJ Badimon L Fuster V Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit J Clin Invest 1990 85 1234 1241 2318976 PMC296557
  31. [38]Nissen SE Tsunoda T Tuzcu EM Schoenhagen P Cooper CJ Yasin M Eaton GM Lauer MA Sheldon WS Grines CL Halpern S Crowe T Blankenship JC Kerensky R Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial JAMA 2003 290 2292 2300 14600188
  32. [39]Betteridge DJ Lipid control in patients with diabetes mellitus Nat Rev Cardiol 8 278 290 21403658

Cited by

Sorted by citations

Authors
Fernández-Hernando, C., & Moore, K. J.
Affiliations
  • From the Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY.
  • NYU Langone Health (US)
ORCID
Moore, Kathryn J.
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-11
Volume
31
Issue
11
Pages
2378-2382
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/atvbaha.111.226688
PMC
PMC3298754
OpenAlex
W2138601349
Cited by
89
References
7
Citations by year
2026: 4 · 2025: 3 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 8 · 2016: 12 · 2015: 12 · 2014: 7 · 2013: 14 · 2012: 5
FWCI
8.50
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG020255)
  • National Heart, Lung, and Blood Institute (R01HL106063, R01HL108182, R01HL107953)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
microRNA, miR-33a, miR-33b, cholesterol homeostasis, SREBP1, SREBP2, fatty acid oxidation, HDL cholesterol, cholesterol export, ABCA1, ABCG1, NPC1, atherosclerosis, dyslipidemia, post-transcriptional regulation, glucose metabolism
MeSH terms
Animals, Cholesterol, Fatty Acids, Glucose, Humans, Models, Animal, MicroRNAs, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review