MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2

Journal article


Publication Details

Author(s): Hinkel R, Trenkwalder T, Petersen B, Husada W, Gesenhues F, Lee S, Hannappel E, Bock-Marquette I, Theisen D, Leitner L, Boekstegers P, Cierniewski C, Mueller OJ, Le Noble F, Adams RH, Weinl C, Nordheim A, Reichart B, Weber C, Olson E, Posern G, Deindl E, Niemann H, Kupatt C
Journal: Nature Communications
Publication year: 2014
Volume: 5
Pages range: 3970
ISSN: 2041-1723


Abstract

Gradual occlusion of coronary arteries may result in reversible loss of cardiomyocyte function (hibernating myocardium), which is amenable to therapeutic neovascularization. The role of myocardin-related transcription factors (MRTFs) co-activating serum response factor (SRF) in this process is largely unknown. Here we show that forced MRTF-A expression induces CCN1 and CCN2 to promote capillary proliferation and pericyte recruitment, respectively. We demonstrate that, upon G-actin binding, thymosin ß4 (Tß4), induces MRTF translocation to the nucleus, SRF-activation and CCN1/2 transcription. In a murine ischaemic hindlimb model, MRTF-A or Tß4 promotes neovascularization, whereas loss of MRTF-A/B or CCN1-function abrogates the Tß4 effect. We further show that, in ischaemic rabbit hindlimbs, MRTF-A as well as Tß4 induce functional neovascularization, and that this process is inhibited by angiopoietin-2, which antagonizes pericyte recruitment. Moreover, MRTF-A improves contractile function of chronic hibernating myocardium of pigs to a level comparable to that of transgenic pigs overexpressing Tß4 (Tß4tg). We conclude that MRTF-A promotes microvessel growth (via CCN1) and maturation (via CCN2), thereby enabling functional improvement of ischaemic muscle tissue.


FAU Authors / FAU Editors

Hannappel, Ewald Prof. Dr.
Professur für Biochemie und Molekulare Neurowissenschaften


External institutions with authors

Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK e.V.)
Eberhard Karls Universität Tübingen
Friedrich-Loeffler-Institut (FLI), Bundesforschungsinstitut für Tiergesundheit
Klinikum der Universität München (Großhadern und Innenstadt)
Ludwig-Maximilians-Universität (LMU)
Martin-Luther-Universität Halle-Wittenberg (MLU)
Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch
Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry
Max-Planck-Institut für molekulare Biomedizin / Max Planck Institute for Molecular Biomedicine
Medical University of Łódź / Uniwersytet Medyczny w Łodzi
Universitätsklinikum Heidelberg
University of Texas Southwestern Medical Center (UT Southwestern)


How to cite

APA:
Hinkel, R., Trenkwalder, T., Petersen, B., Husada, W., Gesenhues, F., Lee, S.,... Kupatt, C. (2014). MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2. Nature Communications, 5, 3970. https://dx.doi.org/10.1038/ncomms4970

MLA:
Hinkel, Rabea, et al. "MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2." Nature Communications 5 (2014): 3970.

BibTeX: 

Last updated on 2018-05-10 at 02:32