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

Autor:	Raaz U; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Schellinger IN; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Chernogubova E; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Warnecke C; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Kayama Y; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Penov K; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Hennigs JK; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Salomons F; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Eken S; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Emrich FC; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Zheng WH; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Adam M; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Jagger A; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Nakagami F; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Toh R; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Toyama K; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Deng A; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Buerke M; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Maegdefessel L; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Hasenfuß G; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Spin JM; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.)., Tsao PS; From the Division of Cardiovascular Medicine (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., F.N., R.T., K.T., A.D., J.M.S., P.S.T.), and Cardiovascular Institute (U.R., Y.K., K.P., J.K.H., F.C.E., M.A., A.J., F.N., K.T., J.M.S., P.S.T.), Stanford University School of Medicine, Stanford, CA; VA Palo Alto Health Care System, Palo Alto, CA (U.R., I.N.S., Y.K., W.H.Z., M.A., A.J., K.T., A.D., J.M.S., P.S.T.); Heart Center, Georg-August-University Göttingen, Göttingen, Germany (U.R., G.H.); Departments of Medicine (E.C., S.E., L.M.) and Cell and Molecular Biology (F.S.), Karolinska Institute, Stockholm, Sweden; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany (C.W.); and Division of Cardiovascular Medicine and Intensive Care Medicine, Saint Mary's Hospital, Siegen, Germany (M.B.). ptsao@stanford.edu.
Jazyk:	angličtina
Zdroj:	Circulation research [Circ Res] 2015 Aug 28; Vol. 117 (6), pp. 513-24. Date of Electronic Publication: 2015 Jul 24.
DOI:	10.1161/CIRCRESAHA.115.306341
Abstrakt:	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. (© 2015 American Heart Association, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu