Abstract
BackgroundIn 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.ObjectivesThis 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.Methods and ResultsTwenty-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).ConclusionsIn 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.
Highlights
Dilated cardiomyopathy (DCM) is one of the most common types of cardiac diseases and is clinically characterized by ventricular chamber dilation and systolic dysfunction that commonly results in ventricular arrhythmias and heart failure (HF) [1]
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
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
Summary
Dilated cardiomyopathy (DCM) is one of the most common types of cardiac diseases and is clinically characterized by ventricular chamber dilation and systolic dysfunction that commonly results in ventricular arrhythmias and heart failure (HF) [1]. New collagen is deposited in an effort to reinforce the ventricle wall, increased activity of matrix metalloproteinases (MMPs) and collagen turnover lead to a deficiency in cross-linking and augmented ECM compliance. This weakening of structural linkages is accompanied by myocyte lengthening, promoting the progression of cardiac dilation, and left ventricular (LV) dysfunction [4,5]. Collagens contribute to the mechanical properties, organization, and morphology of tissues They regulate cell adhesion, proliferation, migration, differentiation, and apoptosis processes, in which transforming growth factor beta-1 (TGF-β1) usually plays a central role in the propagation of intracellular signaling [7,8,9]. We suspect that expression changes in genes coding for non-fibrillar collagens may have a potential role in DCM development.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
