| First Author | Koshman YE | Year | 2015 |
| Journal | J Mol Cell Cardiol | Volume | 89 |
| Issue | Pt B | Pages | 214-22 |
| PubMed ID | 26549358 | Mgi Jnum | J:251204 |
| Mgi Id | MGI:6101557 | Doi | 10.1016/j.yjmcc.2015.11.003 |
| Citation | Koshman YE, et al. (2015) Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy. J Mol Cell Cardiol 89(Pt B):214-22 |
| abstractText | 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. |
