Preferential myofibroblast differentiation of cardiac mesenchymal progenitor cells in the presence of atrial fibrillation

Translational Research

18 December Dec 2017 5 months ago
  • Gambini E, Perrucci GL, Bassetti B, Spaltro G, Pompilio G

Atrial fibrillation (AF) is characterized by electrical, contractile, and structural remodeling mediated by interstitial fibrosis. It has been shown that human cardiac mesenchymal progenitor cells (CMPCs) can be differentiated into endothelial, smooth muscle, and fibroblast cells. Here, we have investigated, for the first time, the contribution of CMPCs in the fibrotic process occurring in AF. As expected, right auricolae samples displayed significantly higher fibrosis in AF vs control (CTR) patients. In tissue samples of AF patients only, double staining for c-kit and the myofibroblast marker α-smooth muscle actin (α-SMA) was detected. The number of c-kit-positive CMPC was higher in atrial subepicardial regions of CTR than AF cells. AF-derived CMPC (AF-CMPC) and CTR-derived CMPC (Ctr-CMPC) were phenotypically similar, except for CD90 and c-kit, which were significantly more present in AF and CTR cells, respectively. Moreover, AF showed a lower rate of population doubling and fold enrichment vs Ctr-CMPC. When exogenously challenged with the profibrotic growth factor TGF-β1 (transforming growth factor-β1), AF-CMPC showed a significantly higher nuclear translocation of SMAD2 than Ctr-CMPC. In addition, TGF-β1 treatment induced the upregulation of COL1A1 and COL1A2 in AF-CMPC only. Further, both a marked production of soluble collagen and α-SMA upregulation have been observed in AF-CMPC only. Finally, electrophysiological studies showed that the inwardly rectifying potassium current (IK1) was evenly present in AF- and Ctr-CMPC in basal conditions and similarly disappeared after TGF-β1 exposure. All together, these data suggest that AF steers the resident atrial CMPC compartment toward an electrically inert profibrotic phenotype.

Reference
Gambini E, Perrucci GL, Bassetti B, Spaltro G, Campostrini G, Lionetti MC, Pilozzi A, Martinelli F, Faruggia A, DiFrancesco D, Barbuti A, Pompilio G. Preferential myofibroblast differentiation of cardiac mesenchymal progenitor cells in the presence of atrial fibrillation. Transl Res 2017 Nov 27. pii: S1931-5244(17)30311-0. doi: 10.1016/j.trsl.2017.11.003. [Epub ahead of print]

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