RSS-Feed abonnieren
DOI: 10.1160/TH11-09-0607
microRNA expression signatures and parallels between monocyte subsets and atherosclerotic plaque in humans
Financial support: This work was supported by the Deutsche Forschungsgemeinschaft (ZE 827/4–1 to A.Z., ZE 827/1–2 to A.Z., WE1913/11–2) and the Leducq Foundation to C.W.Publikationsverlauf
Received:
05. September 2011
Accepted after major revision:
06. Februar 2012
Publikationsdatum:
29. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201204/lookinside/thumbnails/10-1160-th11-09-0607-1.jpg)
Summary
Small non-coding microRNAs (miRNAs) have emerged to play critical roles in cardiovascular biology. Monocytes critically drive atherosclerotic lesion formation, and can be subdivided into a classical and non-classical subset. Here we scrutinised the miRNA signature of human classical and non-classical monocytes, and compared miRNA expression profiles of atherosclerotic plaques from human carotid arteries and healthy arteries. We identified miRNAs to be differentially regulated with a two-fold or higher difference between classical and non-classical monocyte subsets. Moreover, comparing miRNA expression in atherosclerotic plaques compared to healthy arteries, we observed several miRNAs to be aberrantly expressed, with the majority of miRNAs displaying a two-fold or higher increase in plaques and only few miRNAs being decreased. To elucidate similarities in miRNA signatures between monocyte subsets and atherosclerotic plaque, expression of miRNAs highly abundant in monocytes and plaque tissues were compared. Several miRNAs were found in atherosclerotic plaques but not in healthy vessels or either monocyte subset. However, we could identify miRNAs co-expressed in plaque tissue and classical monocytes (miR-99b, miR-152), or non-classical monocytes (miR-422a), or in both monocytes subsets. We thus unravelled candidate miRNAs, which may facilitate our understanding of monocyte recruitment and fate during atherosclerosis, and may serve as therapeutic targets for treating inflammatory vascular diseases.
Note: The editorial process for this article was fully handled by Prof. G. Y. H. Lip, Editor-in-Chief.
These authors contributed equally to this work.
These authors contributed equally to this work.
-
References
- 1 Small EM, Olson EN. Pervasive roles of micrornas in cardiovascular biology. Nature 2011; 469: 336-342.
- 2 Ji R, Cheng Y, Yue J. et al. Microrna expression signature and antisense-mediated depletion reveal an essential role of microrna in vascular neointimal lesion formation. Circ Res 2007; 100: 1579-1588.
- 3 Weber C, Schober A, Zernecke A. Micrornas in arterial remodelling, inflammation and atherosclerosis. Curr Drug Targets 2010; 11: 950-956.
- 4 Rayner KJ, Sheedy FJ, Esau CC. et al. Antagonism of mir-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest 2011; 121: 2921-2931.
- 5 Weber C, Noels H. Atherosclerosis: Current pathogenesis and therapeutic options. Nat Med 2011; 17: 1410-1422.
- 6 Weber C, Zernecke A, Libby P. The multifaceted contributions of leukocyte subsets to atherosclerosis: Lessons from mouse models. Nat Rev Immunol 2008; 08: 802-815.
- 7 Woollard KJ, Geissmann F. Monocytes in atherosclerosis: Subsets and functions. Nat Rev Cardiol 2010; 07: 77-86.
- 8 Gautier EL, Jakubzick C, Randolph GJ. Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis. Arterioscl Thromb Vasc Biol 2009; 29: 1412-1418.
- 9 Swirski FK, Weissleder R, Pittet MJ. Heterogeneous in vivo behavior of monocyte subsets in atherosclerosis. Arterioscl Thromb Vasc Biol 2009; 29: 1424-1432.
- 10 Ingersoll MA, Spanbroek R, Lottaz C. et al. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 2010; 115: e10-19.
- 11 Virmani R, Kolodgie FD, Burke A P. et al. Atherosclerotic plaque progression and vulnerability to rupture: Angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol 2005; 25: 2054-2061.
- 12 Smyth GK. Limma: Linear models for microarray data. Bioinformatics and Computational Biology Solutions using R and Bioconductor. Springer; New York: 2005: 397-420.
- 13 Ihaka R, Gentleman RR. A language for data analysis and graphics. J Comput Graph Stat 1996; 05: 299-314.
- 14 Fichtlscherer S, DeRosa S, Fox H. et al. Circulating micrornas in patients with coronary artery disease. Circ Res 2010; 107: 677-684.
- 15 Tan KS, Armugam A, Sepramaniam S. et al. Expression profile of micrornas in young stroke patients. PLoS One 2009; 04: e7689.
- 16 Latronico M V, Condorelli G. Micrornas and cardiac pathology. Nat Rev Cardiol 2009; 06: 419-429.
- 17 Haver VG, Slart RH, Zeebregts CJ. et al. Rupture of vulnerable atherosclerotic plaques: Micrornas conducting the orchestra?. Trends Cardiovasc Med 2010; 20: 65-71.
- 18 Cordes KR, Sheehy NT, White M P. et al. Mir-145 and mir-143 regulate smooth muscle cell fate and plasticity. Nature 2009; 460: 705-710.
- 19 Zernecke A, Bidzhekov K, Noels H. et al. Delivery of microrna-126 by apoptotic bodies induces cxcl12-dependent vascular protection. Science Signal 2009; 02: ra81.
- 20 Merkerova M, Belickova M, Bruchova H. Differential expression of micrornas in hematopoietic cell lineages. Eur J Haematol 2008; 81: 304-310.
- 21 Li T, Morgan MJ, Choksi S. et al. Micrornas modulate the noncanonical transcription factor nf-kappab pathway by regulating expression of the kinase ikkalpha during macrophage differentiation. Nat Immunol 2010; 11: 799-805.
- 22 Ceppi M, Pereira PM, Dunand-Sauthier I, Barras E, Reith W, Santos MA, Pierre P. Microrna-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci USA 2009; 106: 2735-2740.
- 23 Lu C, Huang X, Zhang X. et al. Mir-221 and mir-155 regulate human dendritic cell development, apoptosis, and il-12 production through targeting of p27kip1, kpc1, and socs-1. Blood 2011; 117: 4293-4303.
- 24 O'Connell RM, Taganov KD, Boldin M P. et al. Microrna-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 2007; 104: 1604-1609.
- 25 Swirski FK, Libby P, Aikawa E. et al. Ly-6chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 2007; 117: 195-205.
- 26 Chen J, Yin H, Jiang Y. et al. Induction of microrna-1 by myocardin in smooth muscle cells inhibits cell proliferation. Arterioscl Thromb Vasc Biol 2011; 31: 368-375.
- 27 Jiang Y, Yin H, Zheng XL. Microrna-1 inhibits myocardin-induced contractility of human vascular smooth muscle cells. J Cell Physiol 2010; 225: 506-511.
- 28 Shen X, Fang J, Lv X. et al. Heparin impairs angiogenesis through inhibition of microrna-10b. J Biol Chem 2011; 286: 26616-26627.
- 29 Small EM, Sutherland LB, Rajagopalan KN. et al. Microrna-218 regulates vascular patterning by modulation of slit-robo signaling. Circ Res 2010; 107: 1336-1344.
- 30 Tserel L, Runnel T, Kisand K. et al. Microrna expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal mir-511 as putative positive regulator of toll-like receptor 4. J Biol Chem 2011; 286: 26487-26495.
- 31 Liu X, Zhan Z, Xu L. et al. Microrna-148/152 impair innate response and antigen presentation of tlr-triggered dendritic cells by targeting camkiialpha. J Immunol 2010; 185: 7244-7251.
- 32 Tacke F, Alvarez D, Kaplan TJ. et al. Monocyte subsets differentially employ ccr2, ccr5, and cx3cr1 to accumulate within atherosclerotic plaques. J Clin Invest 2007; 117: 185-194.
- 33 Song KH, Li T, Owsley E. et al. A putative role of micro rna in regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes. J Lipid Res 2010; 51: 2223-2233.
- 34 Kong KY, Owens KS, Rogers JH. et al. Mir-23a microrna cluster inhibits b-cell development. Exp Hematol. 2010 38. 629-640. e621
- 35 Liu Y, Chen Q, Song Y. et al. Microrna-98 negatively regulates il-10 production and endotoxin tolerance in macrophages after lps stimulation. FEBS Lett 2011; 585: 1963-1968.
- 36 Li LM, Hou DX, Guo YL. et al. Role of microrna-214-targeting phosphatase and tensin homolog in advanced glycation end product-induced apoptosis delay in monocytes. J Immunol 2011; 186: 2552-2560.
- 37 Raitoharju E, Lyytikainen L P, Levula M. et al. 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.