Abstract 1254: Atrial Fibroblasts are Different From Ventricular: Explanation of Atrial-Ventricular Remodeling Differences in Congestive Heart Failure?
Fibroblast responses underlie congestive heart failure (CHF)-induced arrhythmogenic structural remodeling, which is quantitatively different (~20-fold greater) in atria versus ventricles. Atrial-ventricular neurohormonal differences likely contribute; however, we examined the novel hypothesis that there are intrinsic differences between atrial and ventricular fibroblasts (AFb and VFb respectively).
Methods: Morphological characteristics of cultured AFb and VFb were assessed with bright field and confocal microscopy. Growth stimuli-induced proliferation was measured by [3H]thymidine incorporation (N= 5–11 dogs for each protocol; AFb and VFb studied pair-wise for each animal).
Results: Both cell types coexpressed vimentin and αSMA in vitro, indicating a myofibroblast phenotype. AFb behaved differently in culture, with surface area increasing more rapidly than VFb. At confluence, AFb showed more distinct organization and elongated morphology (cell length to width ratio 7.9±0.3 for AFb vs. 2.6±0.2** VFb, **P<0.01). Proliferation of AFb was consistently greater than VFb for a range of growth factors (all values -fold vs baseline): 7% FBS (30.3±5.3 AFb vs 14.2±2.8** VFb); bFGF (2.34±0.37 AFb vs 1.81±0.27* VFb, *p<0.05); AngII (1.92±0.37 AFb vs 1.15±0.10* VFb); ET-1 (1.83±0.32 AFb vs 1.19±0.13* VFb). VFb showed non-significant [3H]thymidine uptake decrease with TGFβ1 stimulation whereas AFb showed a 1.34±0.09* fold increase. Affymetrix gene-microarray analysis revealed 230 differentially expressed transcript probe sets (Q<5*) between AFb and VFb, including extracellular matrix (eg, AFb/VFb expression ratios: fibronectin 4/1, laminin 3/1, collagen 1.9/1, fibulin 3.5/1), cell signalling (wnt receptor 13/1, IGF binding protein 2/1, angiopoietin 0.5/1, VEGF 0.4/1, PDGF 3/1), structural (keratin 0.5/1) and metabolism (xanthine dehyrdogenase 2.5/1) related genes.
Conclusion: AFb are more reactive than VFb, with distinct growth characteristics, proliferative responses and gene expression patterns. These intrinsic AFb-VFb differences are relevant to understanding atrial-ventricular differences in CHF-related fibrosis and designing improved strategies for preventing arrhyth-mogenic atrial structural remodeling.