Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. Signal., 8 December 2009
Vol. 2, Issue 100, p. ra81
[DOI: 10.1126/scisignal.2000610]

RESEARCH ARTICLES

Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection

Alma Zernecke1,2*{dagger}, Kiril Bidzhekov1*, Heidi Noels1*, Erdenechimeg Shagdarsuren1, Lin Gan3, Bernd Denecke3, Mihail Hristov1, Thomas Köppel4, Maliheh Nazari Jahantigh1, Esther Lutgens1,5, Shusheng Wang6, Eric N. Olson6, Andreas Schober1, and Christian Weber1,5{dagger}

1 Institute of Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany.
2 Rudolf-Virchow-Center–DFG Research Center for Experimental Biomedicine, University of Würzburg, 97080 Würzburg, Germany.
3 Interdisciplinary Centre for Clinical Research BIOMAT, Department of Vascular Surgery, RWTH Aachen University, 52074 Aachen, Germany.
4 Department of Vascular Surgery, RWTH Aachen University, 52074 Aachen, Germany.
5 Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, 6200 MD Maastricht, the Netherlands.
6 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390–9148, USA.

* These authors contributed equally to this work.

Abstract: Apoptosis is a pivotal process in embryogenesis and postnatal cell homeostasis and involves the shedding of membranous microvesicles termed apoptotic bodies. In response to tissue damage, the CXC chemokine CXCL12 and its receptor CXCR4 counteract apoptosis and recruit progenitor cells. Here, we show that endothelial cell–derived apoptotic bodies are generated during atherosclerosis and convey paracrine alarm signals to recipient vascular cells that trigger the production of CXCL12. CXCL12 production was mediated by microRNA-126 (miR-126), which was enriched in apoptotic bodies and repressed the function of regulator of G protein (heterotrimeric guanosine triphosphate–binding protein) signaling 16, an inhibitor of G protein–coupled receptor (GPCR) signaling. This enabled CXCR4, a GPCR, to trigger an autoregulatory feedback loop that increased the production of CXCL12. Administration of apoptotic bodies or miR-126 limited atherosclerosis, promoted the incorporation of Sca-1+ progenitor cells, and conferred features of plaque stability on different mouse models of atherosclerosis. This study highlights functions of microRNAs in health and disease that may extend to the recruitment of progenitor cells during other forms of tissue repair or homeostasis.

{dagger} To whom correspondence should be addressed. E-mail: cweber{at}ukaachen.de (C.W.) and alma.zernecke{at}virchow.uni-wuerzburg.de (A.Z.)

Citation: A. Zernecke, K. Bidzhekov, H. Noels, E. Shagdarsuren, L. Gan, B. Denecke, M. Hristov, T. Köppel, M. N. Jahantigh, E. Lutgens, S. Wang, E. N. Olson, A. Schober, C. Weber, Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection. Sci. Signal. 2, ra81 (2009).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Circulating MicroRNAs: Novel Biomarkers and Extracellular Communicators in Cardiovascular Disease?.
E. E. Creemers, A. J. Tijsen, and Y. M. Pinto (2012)
Circ. Res. 110, 483-495
   Abstract »    Full Text »    PDF »
The Use of High-Throughput Technologies to Investigate Vascular Inflammation and Atherosclerosis.
Y. Doring, H. Noels, and C. Weber (2012)
Arterioscler Thromb Vasc Biol 32, 182-195
   Abstract »    Full Text »    PDF »
MicroRNAs are shaping the hematopoietic landscape.
U. Bissels, A. Bosio, and W. Wagner (2012)
Haematologica 97, 160-167
   Abstract »    Full Text »    PDF »
Non-cardiomyocyte microRNAs in heart failure.
A. J. Tijsen, Y. M. Pinto, and E. E. Creemers (2012)
Cardiovasc Res
   Abstract »    Full Text »    PDF »
Leukocyte-Derived Microparticles in Vascular Homeostasis.
A. Angelillo-Scherrer (2012)
Circ. Res. 110, 356-369
   Abstract »    Full Text »    PDF »
Microparticle generation and leucocyte death in Shiga toxin-mediated HUS.
S. Ge, B. Hertel, S. H. Emden, J. Beneke, J. Menne, H. Haller, and S. von Vietinghoff (2012)
Nephrol. Dial. Transplant.
   Abstract »    Full Text »    PDF »
Role of microRNAs in diabetes and its cardiovascular complications.
S. Shantikumar, A. Caporali, and C. Emanueli (2011)
Cardiovasc Res
   Abstract »    Full Text »    PDF »
MicroRNA-126 modulates endothelial SDF-1 expression and mobilization of Sca-1+/Lin- progenitor cells in ischaemia.
C. van Solingen, H. C. de Boer, R. Bijkerk, M. Monge, A. M. van Oeveren-Rietdijk, L. Seghers, M. R. de Vries, E. P. van der Veer, P. H. A. Quax, T. J. Rabelink, et al. (2011)
Cardiovasc Res 92, 449-455
   Abstract »    Full Text »    PDF »
Role of microRNAs in the reperfused myocardium towards post-infarct remodelling.
H. Zhu and G.-C. Fan (2011)
Cardiovasc Res
   Abstract »    Full Text »    PDF »
Small but smart--microRNAs in the centre of inflammatory processes during cardiovascular diseases, the metabolic syndrome, and ageing.
B. Schroen and S. Heymans (2011)
Cardiovasc Res
   Abstract »    Full Text »    PDF »
Profiling of circulating microRNAs: from single biomarkers to re-wired networks.
A. Zampetaki, P. Willeit, I. Drozdov, S. Kiechl, and M. Mayr (2011)
Cardiovasc Res
   Abstract »    Full Text »    PDF »
Circulating MicroRNAs: Biomarkers or Mediators of Cardiovascular Diseases?.
S. Fichtlscherer, A. M. Zeiher, S. Dimmeler, and W. C. Sessa (2011)
Arterioscler Thromb Vasc Biol 31, 2383-2390
   Abstract »    Full Text »    PDF »
Transcoronary Concentration Gradients of Circulating MicroRNAs.
S. De Rosa, S. Fichtlscherer, R. Lehmann, B. Assmus, S. Dimmeler, and A. M. Zeiher (2011)
Circulation 124, 1936-1944
   Abstract »    Full Text »    PDF »
Microparticles, Vascular Function, and Atherothrombosis.
P.-E. Rautou, A.-C. Vion, N. Amabile, G. Chironi, A. Simon, A. Tedgui, and C. M. Boulanger (2011)
Circ. Res. 109, 593-606
   Abstract »    Full Text »    PDF »
Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes.
J.-M. Sinning, J. Losch, K. Walenta, M. Bohm, G. Nickenig, and N. Werner (2011)
Eur. Heart J. 32, 2034-2041
   Abstract »    Full Text »    PDF »
MicroRNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis.
M. Hulsmans, D. De Keyzer, and P. Holvoet (2011)
FASEB J 25, 2515-2527
   Abstract »    Full Text »    PDF »
Microparticles in Angiogenesis: Therapeutic Potential.
M. C. Martinez and R. Andriantsitohaina (2011)
Circ. Res. 109, 110-119
   Abstract »    Full Text »    PDF »
Differential MicroRNA Expression in Experimental Cerebral and Noncerebral Malaria.
F. El-Assaad, C. Hempel, V. Combes, A. J. Mitchell, H. J. Ball, J. A. L. Kurtzhals, N. H. Hunt, J.-M. Mathys, and G. E. R. Grau (2011)
Infect. Immun. 79, 2379-2384
   Abstract »    Full Text »    PDF »
The role of microRNA in modulating myocardial ischemia-reperfusion injury.
Y. Ye, J. R. Perez-Polo, J. Qian, and Y. Birnbaum (2011)
Physiol Genomics 43, 534-542
   Abstract »    Full Text »    PDF »
Human Cardiac Stem Cell Differentiation Is Regulated by a Mircrine Mechanism.
T. Hosoda, H. Zheng, M. Cabral-da-Silva, F. Sanada, N. Ide-Iwata, B. Ogorek, J. Ferreira-Martins, C. Arranto, D. D'Amario, F. del Monte, et al. (2011)
Circulation 123, 1287-1296
   Abstract »    Full Text »    PDF »
Microribonucleic Acids for Prevention of Plaque Rupture and In-Stent Restenosis: "A Finger in the Dam".
J. F. O'Sullivan, K. Martin, and N. M. Caplice (2011)
J. Am. Coll. Cardiol. 57, 383-389
   Abstract »    Full Text »    PDF »
The Many Faces of Endothelial Microparticles.
F. Dignat-George and C. M. Boulanger (2011)
Arterioscler Thromb Vasc Biol 31, 27-33
   Abstract »    Full Text »    PDF »
Circulating microRNAs: novel biomarkers for cardiovascular diseases?.
S. Dimmeler and A. M. Zeiher (2010)
Eur. Heart J. 31, 2705-2707
   Full Text »    PDF »
Intracellular Delivery Strategies for MicroRNAs and Potential Therapies for Human Cardiovascular Diseases.
M. A. Shi and G.-P. Shi (2010)
Science Signaling 3, pe40
   Abstract »    Full Text »    PDF »
Microparticles: Protagonists of a Novel Communication Network for Intercellular Information Exchange.
S. F. Mause and C. Weber (2010)
Circ. Res. 107, 1047-1057
   Abstract »    Full Text »    PDF »
Apoptosis, Stem Cells, and Tissue Regeneration.
A. Bergmann and H. Steller (2010)
Science Signaling 3, re8
   Abstract »    Full Text »    PDF »
Diabetes Mellitus Reveals Its Micro-Signature.
R. Regazzi (2010)
Circ. Res. 107, 686-688
   Full Text »    PDF »
Plasma MicroRNA Profiling Reveals Loss of Endothelial MiR-126 and Other MicroRNAs in Type 2 Diabetes.
A. Zampetaki, S. Kiechl, I. Drozdov, P. Willeit, U. Mayr, M. Prokopi, A. Mayr, S. Weger, F. Oberhollenzer, E. Bonora, et al. (2010)
Circ. Res. 107, 810-817
   Abstract »    Full Text »    PDF »
Circulating MicroRNAs in Patients With Coronary Artery Disease.
S. Fichtlscherer, S. De Rosa, H. Fox, T. Schwietz, A. Fischer, C. Liebetrau, M. Weber, C. W. Hamm, T. Roxe, M. Muller-Ardogan, et al. (2010)
Circ. Res. 107, 677-684
   Abstract »    Full Text »    PDF »
Secretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells.
N. Kosaka, H. Iguchi, Y. Yoshioka, F. Takeshita, Y. Matsuki, and T. Ochiya (2010)
J. Biol. Chem. 285, 17442-17452
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882