Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction

Summary: Myocardial infarction (MI)−induced cardiac fibrosis attenuates cardiac contractile function, and predisposes to arrhythmias and sudden cardiac death. Expression of connective tissue growth factor (CTGF) is elevated in affected organs in virtually every fibrotic disorder and in the diseased...

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Main Authors:	Laura E. Vainio, MD, Zoltán Szabó, MSc, Ruizhu Lin, MSc, Johanna Ulvila, PhD, Raisa Yrjölä, MSc, Tarja Alakoski, MSc, Jarkko Piuhola, MD, PhD, Walter J. Koch, PhD, Heikki Ruskoaho, MD, PhD, Shaun D. Fouse, PhD, Todd W. Seeley, PhD, Erhe Gao, MD, PhD, Pierre Signore, PhD, Kenneth E. Lipson, PhD, Johanna Magga, PhD, Risto Kerkelä, MD, PhD
Format:	Article
Language:	English
Published:	Elsevier 2019-02-01
Series:	JACC: Basic to Translational Science
Online Access:	http://www.sciencedirect.com/science/article/pii/S2452302X18302778

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spelling	doaj-a4c614fa5d9249b080d2fe33ba0c0e4d2020-11-25T01:02:30ZengElsevierJACC: Basic to Translational Science2452-302X2019-02-01418394Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial InfarctionLaura E. Vainio, MD0Zoltán Szabó, MSc1Ruizhu Lin, MSc2Johanna Ulvila, PhD3Raisa Yrjölä, MSc4Tarja Alakoski, MSc5Jarkko Piuhola, MD, PhD6Walter J. Koch, PhD7Heikki Ruskoaho, MD, PhD8Shaun D. Fouse, PhD9Todd W. Seeley, PhD10Erhe Gao, MD, PhD11Pierre Signore, PhD12Kenneth E. Lipson, PhD13Johanna Magga, PhD14Risto Kerkelä, MD, PhD15Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, FinlandResearch Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, FinlandResearch Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, FinlandResearch Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, FinlandResearch Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, FinlandResearch Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, FinlandDivision of Cardiology, Department of Internal Medicine, Oulu University Hospital and University of Oulu, Oulu, FinlandCenter for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PennsylvaniaDivision of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, FinlandFibroGen, Inc., San Francisco, CaliforniaFibroGen, Inc., San Francisco, CaliforniaCenter for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PennsylvaniaFibroGen, Inc., San Francisco, CaliforniaFibroGen, Inc., San Francisco, CaliforniaResearch Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, FinlandResearch Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Address for correspondence: Dr. Risto Kerkelä, Research Unit of Biomedicine, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.Summary: Myocardial infarction (MI)−induced cardiac fibrosis attenuates cardiac contractile function, and predisposes to arrhythmias and sudden cardiac death. Expression of connective tissue growth factor (CTGF) is elevated in affected organs in virtually every fibrotic disorder and in the diseased human myocardium. Mice were subjected to treatment with a CTGF monoclonal antibody (mAb) during infarct repair, post-MI left ventricular (LV) remodeling, or acute ischemia−reperfusion injury. CTGF mAb therapy during infarct repair improved survival and reduced LV dysfunction, and reduced post-MI LV hypertrophy and fibrosis. Mechanistically, CTGF mAb therapy induced expression of cardiac developmental and/or repair genes and attenuated expression of inflammatory and/or fibrotic genes. Key Words: connective tissue growth factor monoclonal antibody, fibrosis, heart failure, ischemia−reperfusion injury, left ventricle, myocardial infarctionhttp://www.sciencedirect.com/science/article/pii/S2452302X18302778
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Laura E. Vainio, MD Zoltán Szabó, MSc Ruizhu Lin, MSc Johanna Ulvila, PhD Raisa Yrjölä, MSc Tarja Alakoski, MSc Jarkko Piuhola, MD, PhD Walter J. Koch, PhD Heikki Ruskoaho, MD, PhD Shaun D. Fouse, PhD Todd W. Seeley, PhD Erhe Gao, MD, PhD Pierre Signore, PhD Kenneth E. Lipson, PhD Johanna Magga, PhD Risto Kerkelä, MD, PhD
spellingShingle	Laura E. Vainio, MD Zoltán Szabó, MSc Ruizhu Lin, MSc Johanna Ulvila, PhD Raisa Yrjölä, MSc Tarja Alakoski, MSc Jarkko Piuhola, MD, PhD Walter J. Koch, PhD Heikki Ruskoaho, MD, PhD Shaun D. Fouse, PhD Todd W. Seeley, PhD Erhe Gao, MD, PhD Pierre Signore, PhD Kenneth E. Lipson, PhD Johanna Magga, PhD Risto Kerkelä, MD, PhD Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction JACC: Basic to Translational Science
author_facet	Laura E. Vainio, MD Zoltán Szabó, MSc Ruizhu Lin, MSc Johanna Ulvila, PhD Raisa Yrjölä, MSc Tarja Alakoski, MSc Jarkko Piuhola, MD, PhD Walter J. Koch, PhD Heikki Ruskoaho, MD, PhD Shaun D. Fouse, PhD Todd W. Seeley, PhD Erhe Gao, MD, PhD Pierre Signore, PhD Kenneth E. Lipson, PhD Johanna Magga, PhD Risto Kerkelä, MD, PhD
author_sort	Laura E. Vainio, MD
title	Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction
title_short	Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction
title_full	Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction
title_fullStr	Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction
title_full_unstemmed	Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction
title_sort	connective tissue growth factor inhibition enhances cardiac repair and limits fibrosis after myocardial infarction
publisher	Elsevier
series	JACC: Basic to Translational Science
issn	2452-302X
publishDate	2019-02-01
description	Summary: Myocardial infarction (MI)−induced cardiac fibrosis attenuates cardiac contractile function, and predisposes to arrhythmias and sudden cardiac death. Expression of connective tissue growth factor (CTGF) is elevated in affected organs in virtually every fibrotic disorder and in the diseased human myocardium. Mice were subjected to treatment with a CTGF monoclonal antibody (mAb) during infarct repair, post-MI left ventricular (LV) remodeling, or acute ischemia−reperfusion injury. CTGF mAb therapy during infarct repair improved survival and reduced LV dysfunction, and reduced post-MI LV hypertrophy and fibrosis. Mechanistically, CTGF mAb therapy induced expression of cardiac developmental and/or repair genes and attenuated expression of inflammatory and/or fibrotic genes. Key Words: connective tissue growth factor monoclonal antibody, fibrosis, heart failure, ischemia−reperfusion injury, left ventricle, myocardial infarction
url	http://www.sciencedirect.com/science/article/pii/S2452302X18302778
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Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction

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