MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2 (2024)

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., Müller, O. J., Le Noble, F., Adams, R. H., Weinl, C., Nordheim, A., Reichart, B., Weber, C., ... Kupatt, C. (2014). MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2. Nature Communications, 5, Article 3970. https://doi.org/10.1038/ncomms4970

Hinkel, Rabea ; Trenkwalder, Teresa ; Petersen, Björn et al. / MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2. In: Nature Communications. 2014 ; Vol. 5.

@article{09856427f4144887895891a2ce403eb2,

title = "MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2",

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 {\ss}4 (T{\ss}4), induces MRTF translocation to the nucleus, SRF-activation and CCN1/2 transcription. In a murine ischaemic hindlimb model, MRTF-A or T{\ss}4 promotes neovascularization, whereas loss of MRTF-A/B or CCN1-function abrogates the T{\ss}4 effect. We further show that, in ischaemic rabbit hindlimbs, MRTF-A as well as T{\ss}4 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 T{\ss}4 (T{\ss}4tg). We conclude that MRTF-A promotes microvessel growth (via CCN1) and maturation (via CCN2), thereby enabling functional improvement of ischaemic muscle tissue.",

author = "Rabea Hinkel and Teresa Trenkwalder and Bj{\"o}rn Petersen and Wira Husada and Florian Gesenhues and Seungmin Lee and Ewald Hannappel and Ildiko Bock-Marquette and Daniel Theisen and Laura Leitner and Peter Boekstegers and Czeslaw Cierniewski and M{\"u}ller, {Oliver J.} and {Le Noble}, Ferdinand and Adams, {Ralf H.} and Christine Weinl and Alfred Nordheim and Bruno Reichart and Christian Weber and Eric Olson and Guido Posern and Elisabeth Deindl and Heiner Niemann and Christian Kupatt",

year = "2014",

month = jun,

day = "9",

doi = "10.1038/ncomms4970",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

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, Müller, OJ, Le Noble, F, Adams, RH, Weinl, C, Nordheim, A, Reichart, B, Weber, C, Olson, E, Posern, G, Deindl, E, Niemann, H 2014, 'MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2', Nature Communications, vol. 5, 3970. https://doi.org/10.1038/ncomms4970

MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2. / Hinkel, Rabea; Trenkwalder, Teresa; Petersen, Björn et al.
In: Nature Communications, Vol. 5, 3970, 09.06.2014.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2

AU - Hinkel, Rabea

AU - Trenkwalder, Teresa

AU - Petersen, Björn

AU - Husada, Wira

AU - Gesenhues, Florian

AU - Lee, Seungmin

AU - Hannappel, Ewald

AU - Bock-Marquette, Ildiko

AU - Theisen, Daniel

AU - Leitner, Laura

AU - Boekstegers, Peter

AU - Cierniewski, Czeslaw

AU - Müller, Oliver J.

AU - Le Noble, Ferdinand

AU - Adams, Ralf H.

AU - Weinl, Christine

AU - Nordheim, Alfred

AU - Reichart, Bruno

AU - Weber, Christian

AU - Olson, Eric

AU - Posern, Guido

AU - Deindl, Elisabeth

AU - Niemann, Heiner

AU - Kupatt, Christian

PY - 2014/6/9

Y1 - 2014/6/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84902248750&partnerID=8YFLogxK

U2 - 10.1038/ncomms4970

DO - 10.1038/ncomms4970

M3 - Article

C2 - 24910328

AN - SCOPUS:84902248750

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 3970

ER -

Hinkel R, Trenkwalder T, Petersen B, Husada W, Gesenhues F, Lee S et al. MRTF-A controls vessel growth and maturation by increasing the expression of CCN1 and CCN2. Nature Communications. 2014 Jun 9;5:3970. doi: 10.1038/ncomms4970