New Altered Non-Fibrillar Collagens in Human Dilated Cardiomyopathy: Role in the Remodeling Process

• Published in: PloS one Vol. 11; no. 12; p. e0168130
• Main Authors: Gil-Cayuela, Carolina, Roselló-LLetí, Esther, Ortega, Ana, Tarazón, Estefanía, Triviño, Juan Carlos, Martínez-Dolz, Luis, González-Juanatey, José Ramón, Lago, Francisca, Portolés, Manuel, Rivera, Miguel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.12.2016; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Apoptosis; Biology and Life Sciences; Biomedical research; Cardiology; Cardiomyopathy; Cardiomyopathy, Dilated - metabolism; Cell adhesion & migration; Collagen; Collagen (type IX); Collagen - metabolism; Congestive cardiomyopathy; Dilated cardiomyopathy; Dilation; Extracellular matrix; Female; Fibrosis; Gene Expression; Gene sequencing; Genes; Growth factors; Heart; Heart diseases; Heart failure; Heart transplantation; Hospitals; Humans; Ischemia; Kinases; Library collections; Male; Medical imaging; Medicine and Health Sciences; Middle Aged; Patients; Polymerase Chain Reaction; Principal components analysis; Research and analysis methods; Ribonucleic acid; RNA; Smooth muscle; Transforming growth factor-b1; Transplantation; Transplants & implants; Ventricle; Ventricular Remodeling; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168130

In dilated cardiomyopathy (DCM), cardiac failure is accompanied by profound alterations of extracellular matrix associated with the progression of cardiac dilation and left ventricular (LV) dysfunction. Recently, we reported alterations of non-fibrillar collagen expression in ischemic cardiomyopathy linked to fibrosis and cardiac remodeling. We suspect that expression changes in genes coding for non-fibrillar collagens may have a potential role in DCM development. This study sought to analyze changes in the expression profile of non-fibrillar collagen genes in patients with DCM and to examine relationships between cardiac remodeling parameters and the expression levels of these genes. Twenty-three human left ventricle tissue samples were obtained from DCM patients (n = 13) undergoing heart transplantation and control donors (n = 10) for RNA sequencing analysis. We found increased mRNA levels of six non-fibrillar collagen genes, such as COL4A5, COL9A1, COL21A1, and COL23A1 (P < 0.05 for all), not previously described in DCM. Protein levels of COL8A1 and COL16A1 (P < 0.05 for both), were correspondingly increased. We also identified TGF-β1 significantly upregulated and related to both COL8A1 and COL16A1. Interestingly, we found a significant relationship between LV mass index and the gene expression level of COL8A1 (r = 0.653, P < 0.05). In our research, we identified new non-fibrillar collagens with altered expression in DCM, being COL8A1 overexpression directly related to LV mass index, suggesting that they may be involved in the progression of cardiac dilation and remodeling.