Abstract 16132: Molecular Differences in Matrix Remodelling in Hfnef and Hfref Patients Suggest Different Entities in Heart Failure
Background: There is little knowledge whether heart failure with normal EF and reduced EF are one single disease or two distinct entities. Here we investigate the differences between both heart failure types in regard gene expression of ECM proteins and matrix metalloproteinases.
Methods: Endomyocardial biopsies were used to culture cardiac fibroblasts from patients with HFNEF as well as HFREF. This human cardiac fibroblast cell culture system from these patients was used to investigate the gene expression pattern under basal conditions as well as after stress stimuli.
Results: In cardiac fibroblasts derived from endomyocardial biopsies of HFNEF patients higher expression of several ECM proteins were detected compared to the HFREF group.
Importantly for LV dilation, the gene expression of the major human collagenase matrix metalloproteinases-1 (MMP-1) was significantly higher expressed in patients with HFREF compared to HFNEF. Moreover, after stimulation with TGF-beta, MMP-1 expression in patients with HFREF increased (2 fold) while this was not the case in HFNEF patients.
Conclusions: In cardiac fibroblasts from patients with HFNEF higher expression levels of ECM proteins were detected compared to HFREF patients which might be one explanation for the stiffer myocardium in HFNEF patients. Furthermore, MMP-1, was higher expressed and could be further increased by TGF-beta stimulation in fibroblasts from patients with HFREF compared to HFNEF. This increment of MMP-1 is important for the destabilisation of the structural integrity of the extracellular matrix in patients with HFREF and therefore triggers cardiac dilation compared to HFNEF patients where no up-regulation of MMP-1 as well as no cardiac dilation could be documented.
This different gene expression between both heart failure types might be one mechanism explaining the differences in the development of HFNEF as well as HFREF and might be one future target for treatment.
- © 2013 by American Heart Association, Inc.