Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy

Research ArticleCardiology Open Access | 10.1172/JCI181630

Bryan Z. Wang,1 Margaretha A.J. Morsink,1 Seong Won Kim,2 Lori J. Luo,1 Xiaokan Zhang,3 Rajesh Kumar Soni,4,5 Roberta I. Lock,1 Jenny Rao,3 Youngbin Kim,1 Anran Zhang,6,7 Meraj Neyazi,2,8,9 Joshua M. Gorham,2 Yuri Kim,2,10 Kemar Brown,2,11 Daniel M. DeLaughter,2 Qi Zhang,2 Barbara McDonough,10,12 Josephine M. Watkins,1 Katherine M. Cunningham,1 Gavin Y. Oudit,6,7 Barry M. Fine,3 Christine E. Seidman,2,10,12 Jonathan G. Seidman,2 and Gordana Vunjak-Novakovic1,3

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Wang, B. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Morsink, M. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Kim, S. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Luo, L. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Zhang, X. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Soni, R. in: JCI | PubMed | Google Scholar |

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Lock, R. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Rao, J. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Kim, Y. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Zhang, A. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Neyazi, M. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Gorham, J. in: JCI | PubMed | Google Scholar |

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Kim, Y. in: JCI | PubMed | Google Scholar |

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Brown, K. in: JCI | PubMed | Google Scholar |

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by DeLaughter, D. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Zhang, Q. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by McDonough, B. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Watkins, J. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Cunningham, K. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Oudit, G. in: JCI | PubMed | Google Scholar |

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Fine, B. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Seidman, C. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, and

5Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

6Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, and

7Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

8Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

9German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.

10Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA.

11Cardiac Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

12Howard Hughes Medical Institute, Bethesda, Maryland, USA.

Address correspondence to: Gordana Vunjak-Novakovic, Department of Biomedical Engineering, Columbia University, 622 West 168th Street VC12-234, New York, New York 10032, USA. Phone: 212.305.5755; Email: gv2131@columbia.edu.

Authorship note: BZW and MAJM contributed equally to this work.

Find articles by Seidman, J. in: JCI | PubMed | Google Scholar

1Department of Biomedical Engineering, Columbia University, New York, New York, USA.

2Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

3Department of Medicine, Columbia University Medical Center, New York, New York, USA.

4Proteomics and Macromolecular Crystallography Shared Resource, Herb

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