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Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus

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Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus. / Raaz, Uwe; Schellinger, Isabel N; Chernogubova, Ekaterina; Warnecke, Christina; Kayama, Yosuke; Penov, Kiril; Hennigs, Jan K; Salomons, Florian; Eken, Suzanne; Emrich, Fabian C; Zheng, Wei H; Adam, Matti; Jagger, Ann; Nakagami, Futoshi; Toh, Ryuji; Toyama, Kensuke; Deng, Alicia; Buerke, Michael; Maegdefessel, Lars; Hasenfuß, Gerd; Spin, Joshua M; Tsao, Philip S.

In: CIRC RES, Vol. 117, No. 6, 28.08.2015, p. 513-24.

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

Harvard

Raaz, U, Schellinger, IN, Chernogubova, E, Warnecke, C, Kayama, Y, Penov, K, Hennigs, JK, Salomons, F, Eken, S, Emrich, FC, Zheng, WH, Adam, M, Jagger, A, Nakagami, F, Toh, R, Toyama, K, Deng, A, Buerke, M, Maegdefessel, L, Hasenfuß, G, Spin, JM & Tsao, PS 2015, 'Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus', CIRC RES, vol. 117, no. 6, pp. 513-24. https://doi.org/10.1161/CIRCRESAHA.115.306341

APA

Raaz, U., Schellinger, I. N., Chernogubova, E., Warnecke, C., Kayama, Y., Penov, K., Hennigs, J. K., Salomons, F., Eken, S., Emrich, F. C., Zheng, W. H., Adam, M., Jagger, A., Nakagami, F., Toh, R., Toyama, K., Deng, A., Buerke, M., Maegdefessel, L., ... Tsao, P. S. (2015). Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus. CIRC RES, 117(6), 513-24. https://doi.org/10.1161/CIRCRESAHA.115.306341

Vancouver

Raaz U, Schellinger IN, Chernogubova E, Warnecke C, Kayama Y, Penov K et al. Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus. CIRC RES. 2015 Aug 28;117(6):513-24. https://doi.org/10.1161/CIRCRESAHA.115.306341

Bibtex

@article{5bc935a4891043d6afa876f7c5bb7218,
title = "Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus",
abstract = "RATIONALE: Accelerated arterial stiffening is a major complication of diabetes mellitus with no specific therapy available to date.OBJECTIVE: The present study investigates the role of the osteogenic transcription factor runt-related transcription factor 2 (Runx2) as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes mellitus.METHODS AND RESULTS: Using a murine model of type 2 diabetes mellitus (db/db mice), we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae, as well as in thoracic aortic samples from patients with type 2 diabetes mellitus. Vascular smooth muscle cell-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that expression of Runx2 in diabetes mellitus is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter.CONCLUSIONS: In conclusion, this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes mellitus, promoting arterial stiffness irrespective of calcification.",
author = "Uwe Raaz and Schellinger, {Isabel N} and Ekaterina Chernogubova and Christina Warnecke and Yosuke Kayama and Kiril Penov and Hennigs, {Jan K} and Florian Salomons and Suzanne Eken and Emrich, {Fabian C} and Zheng, {Wei H} and Matti Adam and Ann Jagger and Futoshi Nakagami and Ryuji Toh and Kensuke Toyama and Alicia Deng and Michael Buerke and Lars Maegdefessel and Gerd Hasenfu{\ss} and Spin, {Joshua M} and Tsao, {Philip S}",
note = "{\textcopyright} 2015 American Heart Association, Inc.",
year = "2015",
month = aug,
day = "28",
doi = "10.1161/CIRCRESAHA.115.306341",
language = "English",
volume = "117",
pages = "513--24",
journal = "CIRC RES",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

RIS

TY - JOUR

T1 - Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes Mellitus

AU - Raaz, Uwe

AU - Schellinger, Isabel N

AU - Chernogubova, Ekaterina

AU - Warnecke, Christina

AU - Kayama, Yosuke

AU - Penov, Kiril

AU - Hennigs, Jan K

AU - Salomons, Florian

AU - Eken, Suzanne

AU - Emrich, Fabian C

AU - Zheng, Wei H

AU - Adam, Matti

AU - Jagger, Ann

AU - Nakagami, Futoshi

AU - Toh, Ryuji

AU - Toyama, Kensuke

AU - Deng, Alicia

AU - Buerke, Michael

AU - Maegdefessel, Lars

AU - Hasenfuß, Gerd

AU - Spin, Joshua M

AU - Tsao, Philip S

N1 - © 2015 American Heart Association, Inc.

PY - 2015/8/28

Y1 - 2015/8/28

N2 - RATIONALE: Accelerated arterial stiffening is a major complication of diabetes mellitus with no specific therapy available to date.OBJECTIVE: The present study investigates the role of the osteogenic transcription factor runt-related transcription factor 2 (Runx2) as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes mellitus.METHODS AND RESULTS: Using a murine model of type 2 diabetes mellitus (db/db mice), we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae, as well as in thoracic aortic samples from patients with type 2 diabetes mellitus. Vascular smooth muscle cell-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that expression of Runx2 in diabetes mellitus is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter.CONCLUSIONS: In conclusion, this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes mellitus, promoting arterial stiffness irrespective of calcification.

AB - RATIONALE: Accelerated arterial stiffening is a major complication of diabetes mellitus with no specific therapy available to date.OBJECTIVE: The present study investigates the role of the osteogenic transcription factor runt-related transcription factor 2 (Runx2) as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes mellitus.METHODS AND RESULTS: Using a murine model of type 2 diabetes mellitus (db/db mice), we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae, as well as in thoracic aortic samples from patients with type 2 diabetes mellitus. Vascular smooth muscle cell-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that expression of Runx2 in diabetes mellitus is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter.CONCLUSIONS: In conclusion, this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes mellitus, promoting arterial stiffness irrespective of calcification.

U2 - 10.1161/CIRCRESAHA.115.306341

DO - 10.1161/CIRCRESAHA.115.306341

M3 - SCORING: Journal article

C2 - 26208651

VL - 117

SP - 513

EP - 524

JO - CIRC RES

JF - CIRC RES

SN - 0009-7330

IS - 6

ER -