Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a

Circulation Research

Volumn 121, Issue 4, 2017, Pages 354-367

  Cheng, Henry S ^a,b,c   Besla, Rickvinder ^a,b,c   Li, Angela ^a,b,c   Chen, Zhiqi ^a,b,c   Shikatani, Eric A ^a,b,c   Nazari Jahantigh, Maliheh ^a,d   Hammoutène, Adel ^e   Nguyen, My Anh ^f   Geoffrion, Michele ^f   Cai, Lei ^g   Khyzha, Nadiya ^b,c   Li, Tong ^g   Macparland, Sonya A ^a,b   Husain, Mansoor ^a,b,c   Cybulsky, Myron I ^a,b,c   Boulanger, Chantal M ^e   Temel, Ryan E ^g   Schober, Andreas ^d   Rayner, Katey J ^f   Robbins, Clinton S ^a,b,c   Fish, Jason E ^a,b,c   more..

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c HEART AND STROKE FOUNDATION OF CANADA   (Canada)

^d LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^e PARIS CARDIOVASCULAR RESEARCH CENTER   (France)

^f UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

^g UNIVERSITY OF KENTUCKY   (United States)

Author keywords

atherosclerosis; endothelial cells; hematopoiesis; inflammation; microRNAs

Indexed keywords

ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MICRORNA 146A; SORTILIN; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR; VASCULAR CELL ADHESION MOLECULE 1; VERY LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; MICRORNA; MIRN146 MICRORNA, MOUSE; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL;

AGE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; B LYMPHOCYTE; BONE MARROW DEPRESSION; BONE MARROW TRANSPLANTATION; CELL ACTIVATION; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL METABOLISM; COLONY FORMING UNIT GM; CONTROLLED STUDY; DIET; ENDOTHELIUM CELL; EXTRAMEDULLARY HEMATOPOIESIS; FEMALE; GENE DELETION; HEMATOPOIESIS; INFLAMMATION; LEUKOCYTE; LOW DENSITY LIPOPROTEIN RECEPTOR KO MOUSE; LYMPHOCYTE; MACROPHAGE; MALE; MONOCYTE; MOUSE; MULTIPOTENT STEM CELL; MYELOID PROGENITOR CELL; NEUTROPHIL; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SPLENOMEGALY; THORACIC AORTA; VASCULAR ENDOTHELIUM; VASCULARIZATION; ADVERSE EFFECTS; ANIMAL; ATHEROGENIC DIET; BONE MARROW CELL; BOVINE; C57BL MOUSE; GENETICS; KNOCKOUT MOUSE; METABOLISM; PATHOLOGY;

ANIMALS; ATHEROSCLEROSIS; BONE MARROW CELLS; CATTLE; CHOLESTEROL, VLDL; DIET, ATHEROGENIC; ENDOTHELIAL CELLS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICRORNAS; RECEPTORS, LDL;

EID: 85026812154     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.116.310529     Document Type: Article

References (44)

1. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685-1695. doi: 10.1056/NEJMra043430.
2. Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011;17:1410-1422. doi: 10.1038/nm.2538.
3. Gareus R, Kotsaki E, Xanthoulea S, van der Made I, Gijbels MJ, Kardakaris R, Polykratis A, Kollias G, de Winther MP, Pasparakis M. Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis. Cell Metab. 2008;8:372-383. doi: 10.1016/j.cmet.2008.08.016.
4. Kempe S, Kestler H, Lasar A, Wirth T. NF-kappaB controls the global proinflammatory response in endothelial cells: evidence for the regulation of a pro-atherogenic program. Nucleic Acids Res. 2005;33:5308-5319. doi: 10.1093/nar/gki836.
5. Cheng HS, Njock MS, Khyzha N, Dang LT, Fish JE. Noncoding RNAs regulate NF-κB signaling to modulate blood vessel inflammation. Front Genet. 2014;5:422. doi: 10.3389/fgene.2014.00422.
6. Cheng HS, Sivachandran N, Lau A, Boudreau E, Zhao JL, Baltimore D, Delgado-Olguin P, Cybulsky MI, Fish JE. MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Mol Med. 2013;5:1017-1034. doi: 10.1002/emmm.201202318.
7. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaBdependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006;103:12481-12486. doi: 10.1073/pnas.0605298103.
8. Zhao JL, Rao DS, Boldin MP, Taganov KD, O'Connell RM, Baltimore D. NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proc Natl Acad Sci USA. 2011;108:9184-9189. doi: 10.1073/pnas.1105398108.
9. Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, Garcia- Flores Y, Luong M, Devrekanli A, Xu J, Sun G, Tay J, Linsley PS, Baltimore D. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med. 2011;208:1189-1201. doi: 10.1084/jem.20101823.
10. Zhao JL, Rao DS, O'Connell RM, Garcia-Flores Y, Baltimore D. MicroRNA-146a acts as a guardian of the quality and longevity of hematopoietic stem cells in mice. Elife. 2013;2:e00537. doi: 10.7554/ eLife.00537.
11. Etzrodt M, Cortez-Retamozo V, Newton A, et al. Regulation of monocyte functional heterogeneity by miR-146a and Relb. Cell Rep. 2012;1:317-324. doi: 10.1016/j.celrep.2012.02.009.
12. Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, Page M, Kaltschmidt C, Baeuerle PA, Neumeier D. Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest. 1996;97:1715-1722. doi: 10.1172/JCI118598.
13. Kanters E, Pasparakis M, Gijbels MJ, Vergouwe MN, Partouns-Hendriks I, Fijneman RJ, Clausen BE, Förster I, Kockx MM, Rajewsky K, Kraal G, Hofker MH, de Winther MP. Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 2003;112:1176-1185. doi: 10.1172/JCI18580.
14. Li K, Ching D, Luk FS, Raffai RL. Apolipoprotein E enhances microRNA- 146a in monocytes and macrophages to suppress nuclear factor-κBdriven inflammation and atherosclerosis. Circ Res. 2015;117:e1-e11. doi: 10.1161/CIRCRESAHA.117.305844.
15. Von Der Thüsen JH, Kuiper J, Fekkes ML, De Vos P, Van Berkel TJ, Biessen EA. Attenuation of atherogenesis by systemic and local adenovirus- mediated gene transfer of interleukin-10 in LDLr-/- mice. FASEB J. 2001;15:2730-2732. doi: 10.1096/fj.01-0483fje.
16. Hashizume M, Yoshida H, Koike N, Suzuki M, Mihara M. Overproduced interleukin 6 decreases blood lipid levels via upregulation of very-lowdensity lipoprotein receptor. Ann Rheum Dis. 2010;69:741-746. doi: 10.1136/ard.2008.104844.
17. Lehtimäki T, Ojala P, Rontu R, Goebeler S, Karhunen PJ, Jylhä M, Mattila K, Metso S, Jokela H, Nikkilä M, Wuolijoki E, Hervonen A, Hurme M. Interleukin-6 modulates plasma cholesterol and C-reactive protein concentrations in nonagenarians. J Am Geriatr Soc. 2005;53:1552-1558. doi: 10.1111/j.1532-5415.2005.53484.x.
18. Musunuru K, Strong A, Frank-Kamenetsky M, et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature. 2010;466:714-719. doi: 10.1038/nature09266.
19. Mortensen MB, Kjolby M, Gunnersen S, Larsen JV, Palmfeldt J, Falk E, Nykjaer A, Bentzon JF. Targeting sortilin in immune cells reduces proinflammatory cytokines and atherosclerosis. J Clin Invest. 2014;124:5317-5322. doi: 10.1172/JCI76002.
20. Robbins CS, Chudnovskiy A, Rauch PJ, et al. Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions. Circulation. 2012;125:364-374. doi: 10.1161/ CIRCULATIONAHA.111.061986.
21. Aviram M, Brook JG, Tatarsky I, Levy Y, Carter A. Increased low-density lipoprotein levels after splenectomy: a role for the spleen in cholesterol metabolism in myeloproliferative disorders. Am J Med Sci. 1986;291:25-28.
22. Rezzoug F, Huang Y, Tanner MK, Wysoczynski M, Schanie CL, Chilton PM, Ratajczak MZ, Fugier-Vivier IJ, Ildstad ST. TNF-alpha is critical to facilitate hemopoietic stem cell engraftment and function. J Immunol. 2008;180:49-57.
23. Baldridge MT, King KY, Goodell MA. Inflammatory signals regulate hematopoietic stem cells. Trends Immunol. 2011;32:57-65. doi: 10.1016/j. it.2010.12.003.
24. Yang L, Boldin MP, Yu Y, Liu CS, Ea CK, Ramakrishnan P, Taganov KD, Zhao JL, Baltimore D. miR-146a controls the resolution of T cell responses in mice. J Exp Med. 2012;209:1655-1670. doi: 10.1084/ jem.20112218.
25. Raitoharju E, Lyytikäinen LP, Levula M, Oksala N, Mennander A, Tarkka M, Klopp N, Illig T, Kähönen M, Karhunen PJ, Laaksonen R, Lehtimäki T. miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the Tampere Vascular Study. Atherosclerosis. 2011;219:211-217. doi: 10.1016/j.atherosclerosis.2011.07.020.
26. Bao MH, Xiao Y, Zhang QS, Luo HQ, Luo J, Zhao J, Li GY, Zeng J, Li JM. Meta-analysis of miR-146a polymorphisms association with coronary artery diseases and ischemic stroke. Int J Mol Sci. 2015;16:14305-14317. doi: 10.3390/ijms160714305.
27. He Y, Yang J, Kong D, Lin J, Xu C, Ren H, Ouyang P, Ding Y, Wang K. Association of miR-146a rs2910164 polymorphism with cardiocerebrovascular diseases: a systematic review and meta-analysis. Gene. 2015;565:171-179. doi: 10.1016/j.gene.2015.04.020.
28. Ramkaran P, Khan S, Phulukdaree A, Moodley D, Chuturgoon AA. miR- 146a polymorphism influences levels of miR-146a, IRAK-1, and TRAF- 6 in young patients with coronary artery disease. Cell Biochem Biophys. 2014;68:259-266. doi: 10.1007/s12013-013-9704-7.
29. Xiong XD, Cho M, Cai XP, Cheng J, Jing X, Cen JM, Liu X, Yang XL, Suh Y. A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression. Mutat Res. 2014;761:15-20. doi: 10.1016/j.mrfmmm.2014.01.001.
30. Ma X, Feng Y. Hypercholesterolemia tunes hematopoietic stem/progenitor cells for inflammation and atherosclerosis. Int J Mol Sci. 2016;17:E1162.
31. Murphy AJ, Tall AR. Disordered haematopoiesis and athero-thrombosis. Eur Heart J. 2016;37:1113-1121. doi: 10.1093/eurheartj/ehv718.
32. Feng Y, Schouteden S, Geenens R, Van Duppen V, Herijgers P, Holvoet P, Van Veldhoven PP, Verfaillie CM. Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice. PLoS One. 2012;7:e47286. doi: 10.1371/ journal.pone.0047286.
33. Soehnlein O, Swirski FK. Hypercholesterolemia links hematopoiesis with atherosclerosis. Trends Endocrinol Metab. 2013;24:129-136. doi: 10.1016/j.tem.2012.10.008.
34. Ye YX, Calcagno C, Binderup T, et al. Imaging macrophage and hematopoietic progenitor proliferation in atherosclerosis. Circ Res. 2015;117:835-845. doi: 10.1161/CIRCRESAHA.115.307024.
35. Westerterp M, Gourion-Arsiquaud S, Murphy AJ, Shih A, Cremers S, Levine RL, Tall AR, Yvan-Charvet L. Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways. Cell Stem Cell. 2012;11:195-206. doi: 10.1016/j.stem.2012.04.024.
36. Tie G, Messina KE, Yan J, Messina JA, Messina LM. Hypercholesterolemia induces oxidant stress that accelerates the ageing of hematopoietic stem cells. J Am Heart Assoc. 2014;3:e000241. doi: 10.1161/JAHA.113.000241.
37. Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, Osterreicher CH, Takahashi H, Karin M. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell. 2010;140:197-208. doi: 10.1016/j.cell.2009.12.052.
38. Glund S, Krook A. Role of interleukin-6 signalling in glucose and lipid metabolism. Acta Physiol. 2008;192:37-48. doi: 10.1111/j.1748-1716.2007.01779.x.
39. Murthy S, Mathur S, Bishop WP, Field EJ. Inhibition of apolipoprotein B secretion by IL-6 is mediated by EGF or an EGF-like molecule in CaCo-2 cells. J Lipid Res. 1997;38:206-216.
40. Westerterp M, Tall AR. SORTILIN: many headed hydra. Circ Res. 2015;116:764-766. doi: 10.1161/CIRCRESAHA.115.306036.
41. Strong A, Ding Q, Edmondson AC, et al. Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism. J Clin Invest. 2012;122:2807-2816. doi: 10.1172/JCI63563.
42. Kjolby M, Andersen OM, Breiderhoff T, Fjorback AW, Pedersen KM, Madsen P, Jansen P, Heeren J, Willnow TE, Nykjaer A. Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export. Cell Metab. 2010;12:213-223. doi: 10.1016/j.cmet.2010.08.006.
43. Patel KM, Strong A, Tohyama J, Jin X, Morales CR, Billheimer J, Millar J, Kruth H, Rader DJ. Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis. Circ Res. 2015;116:789-796. doi: 10.1161/CIRCRESAHA.116.305811.
44. Ma S, Tian XY, Zhang Y, Mu C, Shen H, Bismuth J, Pownall HJ, Huang Y, Wong WT. E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis. Sci Rep. 2016;6:22910. doi: 10.1038/srep22910.