miR-21 promotes fibrosis in an acute cardiac allograft transplantation model

Shashi Kumar Gupta; Ryo Itagaki; Xiang Zheng; Sandor Batkai; Sabrina Thum; Fareed Ahmad; Lucas N Van Aelst; Amit Sharma; Maria-Teresa Piccoli; Florian Weinberger; Jan Fiedler; Michael Heuser; Stephane Heymans; Christine S Falk; Reinhold Förster; Sonja Schrepfer; Thomas Thum

doi:10.1093/cvr/cvw030

miR-21 promotes fibrosis in an acute cardiac allograft transplantation model

Standard

miR-21 promotes fibrosis in an acute cardiac allograft transplantation model. / Gupta, Shashi Kumar; Itagaki, Ryo; Zheng, Xiang; Batkai, Sandor; Thum, Sabrina; Ahmad, Fareed; Van Aelst, Lucas N; Sharma, Amit; Piccoli, Maria-Teresa; Weinberger, Florian; Fiedler, Jan; Heuser, Michael; Heymans, Stephane; Falk, Christine S; Förster, Reinhold; Schrepfer, Sonja; Thum, Thomas.

In: CARDIOVASC RES, Vol. 110, No. 2, 15.05.2016, p. 215-226.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gupta, SK, Itagaki, R, Zheng, X, Batkai, S, Thum, S, Ahmad, F, Van Aelst, LN, Sharma, A, Piccoli, M-T, Weinberger, F, Fiedler, J, Heuser, M, Heymans, S, Falk, CS, Förster, R, Schrepfer, S & Thum, T 2016, 'miR-21 promotes fibrosis in an acute cardiac allograft transplantation model', CARDIOVASC RES, vol. 110, no. 2, pp. 215-226. https://doi.org/10.1093/cvr/cvw030

APA

Gupta, S. K., Itagaki, R., Zheng, X., Batkai, S., Thum, S., Ahmad, F., Van Aelst, L. N., Sharma, A., Piccoli, M-T., Weinberger, F., Fiedler, J., Heuser, M., Heymans, S., Falk, C. S., Förster, R., Schrepfer, S., & Thum, T. (2016). miR-21 promotes fibrosis in an acute cardiac allograft transplantation model. CARDIOVASC RES, 110(2), 215-226. https://doi.org/10.1093/cvr/cvw030

Vancouver

Gupta SK, Itagaki R, Zheng X, Batkai S, Thum S, Ahmad F et al. miR-21 promotes fibrosis in an acute cardiac allograft transplantation model. CARDIOVASC RES. 2016 May 15;110(2):215-226. https://doi.org/10.1093/cvr/cvw030

Bibtex

@article{d64e31ee4af8452da497b672748cef8f,

title = "miR-21 promotes fibrosis in an acute cardiac allograft transplantation model",

abstract = "AIMS: Cardiac transplantation is the only curative therapy for end-stage heart failure. Fibrosis is one of the major causes for impaired function of cardiac allografts. MicroRNAs, a class of small non-coding RNAs, play a critical role in the development of cardiovascular disease, but the role of microRNAs in cardiac allograft failure is not well understood.METHODS AND RESULTS: To uncover a role of microRNAs during cardiac graft fibrosis, we generated global microRNA profiles in allogeneic (BALB/c in C57BL/6N) and isogeneic (C57BL/6N in C57BL/6N) murine hearts after transplantation. miR-21 together with cardiac fibrosis was increased in cardiac allografts compared with isografts. Likewise, patients with cardiac rejection after heart transplantation showed increased cardiac miR-21 levels. miR-21 was induced upon treatment with IL-6 in a monocyte cell line. Overexpression of miR-21 in this monocyte cell line activated a fibrotic gene programme and promoted monocyte-to-fibrocyte transition together with activation of chemokine (C-C) motif ligand 2 (monocyte chemoattractant protein 1) via the phosphatase and tensin homologue/activator protein 1 regulatory axis. In vivo, both genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in cardiac allografts.CONCLUSION: Thus, inhibition of miR-21 is a novel strategy to target fibrosis development in cardiac allografts.",

keywords = "Journal Article, Research Support, Non-U.S. Gov't",

author = "Gupta, {Shashi Kumar} and Ryo Itagaki and Xiang Zheng and Sandor Batkai and Sabrina Thum and Fareed Ahmad and {Van Aelst}, {Lucas N} and Amit Sharma and Maria-Teresa Piccoli and Florian Weinberger and Jan Fiedler and Michael Heuser and Stephane Heymans and Falk, {Christine S} and Reinhold F{\"o}rster and Sonja Schrepfer and Thomas Thum",

year = "2016",

month = may,

day = "15",

doi = "10.1093/cvr/cvw030",

language = "English",

volume = "110",

pages = "215--226",

journal = "CARDIOVASC RES",

issn = "0008-6363",

publisher = "Oxford University Press",

number = "2",

}

RIS

TY - JOUR

T1 - miR-21 promotes fibrosis in an acute cardiac allograft transplantation model

AU - Gupta, Shashi Kumar

AU - Itagaki, Ryo

AU - Zheng, Xiang

AU - Batkai, Sandor

AU - Thum, Sabrina

AU - Ahmad, Fareed

AU - Van Aelst, Lucas N

AU - Sharma, Amit

AU - Piccoli, Maria-Teresa

AU - Weinberger, Florian

AU - Fiedler, Jan

AU - Heuser, Michael

AU - Heymans, Stephane

AU - Falk, Christine S

AU - Förster, Reinhold

AU - Schrepfer, Sonja

AU - Thum, Thomas

PY - 2016/5/15

Y1 - 2016/5/15

N2 - AIMS: Cardiac transplantation is the only curative therapy for end-stage heart failure. Fibrosis is one of the major causes for impaired function of cardiac allografts. MicroRNAs, a class of small non-coding RNAs, play a critical role in the development of cardiovascular disease, but the role of microRNAs in cardiac allograft failure is not well understood.METHODS AND RESULTS: To uncover a role of microRNAs during cardiac graft fibrosis, we generated global microRNA profiles in allogeneic (BALB/c in C57BL/6N) and isogeneic (C57BL/6N in C57BL/6N) murine hearts after transplantation. miR-21 together with cardiac fibrosis was increased in cardiac allografts compared with isografts. Likewise, patients with cardiac rejection after heart transplantation showed increased cardiac miR-21 levels. miR-21 was induced upon treatment with IL-6 in a monocyte cell line. Overexpression of miR-21 in this monocyte cell line activated a fibrotic gene programme and promoted monocyte-to-fibrocyte transition together with activation of chemokine (C-C) motif ligand 2 (monocyte chemoattractant protein 1) via the phosphatase and tensin homologue/activator protein 1 regulatory axis. In vivo, both genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in cardiac allografts.CONCLUSION: Thus, inhibition of miR-21 is a novel strategy to target fibrosis development in cardiac allografts.

AB - AIMS: Cardiac transplantation is the only curative therapy for end-stage heart failure. Fibrosis is one of the major causes for impaired function of cardiac allografts. MicroRNAs, a class of small non-coding RNAs, play a critical role in the development of cardiovascular disease, but the role of microRNAs in cardiac allograft failure is not well understood.METHODS AND RESULTS: To uncover a role of microRNAs during cardiac graft fibrosis, we generated global microRNA profiles in allogeneic (BALB/c in C57BL/6N) and isogeneic (C57BL/6N in C57BL/6N) murine hearts after transplantation. miR-21 together with cardiac fibrosis was increased in cardiac allografts compared with isografts. Likewise, patients with cardiac rejection after heart transplantation showed increased cardiac miR-21 levels. miR-21 was induced upon treatment with IL-6 in a monocyte cell line. Overexpression of miR-21 in this monocyte cell line activated a fibrotic gene programme and promoted monocyte-to-fibrocyte transition together with activation of chemokine (C-C) motif ligand 2 (monocyte chemoattractant protein 1) via the phosphatase and tensin homologue/activator protein 1 regulatory axis. In vivo, both genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in cardiac allografts.CONCLUSION: Thus, inhibition of miR-21 is a novel strategy to target fibrosis development in cardiac allografts.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/cvr/cvw030

DO - 10.1093/cvr/cvw030

M3 - SCORING: Journal article

C2 - 26865549

VL - 110

SP - 215

EP - 226

JO - CARDIOVASC RES

JF - CARDIOVASC RES

SN - 0008-6363

IS - 2

ER -