Key result
Dilated cardiomyopathy was associated with significantly increased mRNA and protein levels of non-fibrillar collagens, including COL8A1 and COL16A1, with COL8A1 overexpression directly correlating with left ventricular mass index.
Cross-Sectional (n=38)
No
Effect estimate: Increased mRNA levels (≥1.5-fold)
p-value: p=<0.05
Overexpression of non-fibrillar collagens, particularly COL8A1, is associated with left ventricular mass index in dilated cardiomyopathy, suggesting a role in cardiac remodeling.
COL8A1 overexpression may mark remodeling severity in dilated cardiomyopathy; hypothesis-generating and requires prospective validation before clinical consideration.
BACKGROUND: 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. OBJECTIVES: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.
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Gil‐Cayuela et al. (2016) conducted a cross-sectional in Dilated Cardiomyopathy (n=38). Dilated cardiomyopathy vs. Non-diseased controls was evaluated on mRNA levels of non-fibrillar collagen genes (COL4A5, COL8A1, COL9A1, COL16A1, COL21A1, and COL23A1) (Increased mRNA levels (≥1.5-fold), p=<0.05). Dilated cardiomyopathy was associated with significantly increased mRNA and protein levels of non-fibrillar collagens, including COL8A1 and COL16A1, with COL8A1 overexpression directly correlating with left ventricular mass index.
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