Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy Journal Article

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Authors: Koshman, Y. E.; Sternlicht, M. D.; Kim, T.; O'Hara, C. P.; Koczor, C. A.; Lewis, W.; Seeley, T. W.; Lipson, K. E.; Samarel, A. M.
Article Title: Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy
Abstract: Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective tissue growth factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. Our aim was to test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cepsilon (PKCepsilon) mouse model of DCM. Transgenic mice expressing constitutively active PKCepsilon in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to cardiac fibrosis, heart failure, and increased mortality. Beginning at 3 months of age, PKCepsilon mice were treated with a neutralizing monoclonal antibody to CTGF (FG-3149) for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic functions in PKCepsilon mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling was elevated in PKCepsilon mice, but significantly decreased by CTGF inhibition. However total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCepsilon mice suggests that CTGF inhibition may benefit patients with DCM. Additional studies to explore this potential are warranted.
Journal Title: Journal of Molecular and Cellular Cardiology
Volume: 89
Issue: Pt B
ISSN: 1095-8584; 0022-2828
Publisher: Unknown  
Journal Place: England
Date Published: 2015
Start Page: 214
End Page: 222
Language: eng
DOI/URL:

10.1016/j.yjmcc.2015.11.003
Notes: LR: 20151224; CI: Copyright (c) 2015; GR: 1F32 HL096143/HL/NHLBI NIH HHS/United States; GR: F32 HL096143/HL/NHLBI NIH HHS/United States; GR: P01 HL062426/HL/NHLBI NIH HHS/United States; GR: P01 HL62426/HL/NHLBI NIH HHS/United States; GR: R01 DA-030996/DA/NIDA NIH HHS/United States; GR: R01 DA030996/DA/NIDA NIH HHS/United States; JID: 0262322; NIHMS737647; OID: NLM: NIHMS737647 [Available on 12/01/16]; OID: NLM: PMC4689630 [Available on 12/01/16]; OTO: NOTNLM; PMCR: 2016/12/01 00:00; 2015/08/24 [received]; 2015/10/20 [revised]; 2015/11/02 [accepted]; 2015/11/05 [aheadofprint]; ppublish