title: New Altered Non-Fibrillar Collagens in Human Dilated Cardiomyopathy: Role in the Remodeling Process.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gil-Cayuela
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló-LLetí
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Tarazón
authors.affiliation: Genomic Systems, Paterna (Valencia), Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Triviño
authors.affiliation: Heart Failure and Transplantation Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Dolz
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
authors.affiliation: Cardiocirculatory Unit, Health Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020257:Ventricular Remodeling
chemical_list: D003094:Collagen