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Usage Information

Cadherin-11 blockade reduces inflammation-driven fibrotic remodeling and improves outcomes after myocardial infarction
Alison K. Schroer, … , Hind Lal, W. David Merryman
Alison K. Schroer, … , Hind Lal, W. David Merryman
Published September 19, 2019
Citation Information: JCI Insight. 2019;4(18):e131545. https://doi.org/10.1172/jci.insight.131545.
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Research Article Cardiology

Cadherin-11 blockade reduces inflammation-driven fibrotic remodeling and improves outcomes after myocardial infarction

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Abstract

Over one million Americans experience myocardial infarction (MI) annually, and the resulting scar and subsequent cardiac fibrosis gives rise to heart failure. A specialized cell-cell adhesion protein, cadherin-11 (CDH11), contributes to inflammation and fibrosis in rheumatoid arthritis, pulmonary fibrosis, and aortic valve calcification but has not been studied in myocardium after MI. MI was induced by ligation of the left anterior descending artery in mice with either heterozygous or homozygous knockout of CDH11, wild-type mice receiving bone marrow transplants from Cdh11-deficient animals, and wild-type mice treated with a functional blocking antibody against CDH11 (SYN0012). Flow cytometry revealed significant CDH11 expression in noncardiomyocyte cells after MI. Animals given SYN0012 had improved cardiac function, as measured by echocardiogram, reduced tissue remodeling, and altered transcription of inflammatory and proangiogenic genes. Targeting CDH11 reduced bone marrow–derived myeloid cells and increased proangiogenic cells in the heart 3 days after MI. Cardiac fibroblast and macrophage interactions increased IL-6 secretion in vitro. Our findings suggest that CDH11-expressing cells contribute to inflammation-driven fibrotic remodeling after MI and that targeting CDH11 with a blocking antibody improves outcomes by altering recruitment of bone marrow–derived cells, limiting the macrophage-induced expression of IL-6 by fibroblasts and promoting vascularization.

Authors

Alison K. Schroer, Matthew R. Bersi, Cynthia R. Clark, Qinkun Zhang, Lehanna H. Sanders, Antonis K. Hatzopoulos, Thomas L. Force, Susan M. Majka, Hind Lal, W. David Merryman

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Usage data is cumulative from July 2021 through July 2022.

Usage JCI PMC
Text version 1,678 533
PDF 107 50
Figure 214 3
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Citation downloads 39 0
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Total Views 2,747

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