Protective role of 5-azacytidine on myocardial infarction is associated with modulation of macrophage phenotype and inhibition of fibrosis.
Bottom Line: Nitric oxide was produced by PGN, which was reduced by 77.87% after 5AZ treatment.Cardiac fibrosis in the MI+5AZ was 8.14 ± 1.00%, compared with 14.93 ± 2.98% in the MI group (P < 0.05).In cardiac fibroblasts, pro-fibrotic mediators and cell proliferation were increased by AngII, and these increases were attenuated after 5AZ treatment. 5AZ exerts its cardiac protective role through modulation of macrophages and cardiac fibroblasts.
Affiliation: Heart Research Center, Chonnam National University Hospital, Gwangju, South Korea.Show MeSH
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Mentions: Because iNOS is a well-known target of NF-κB, the NF-κB response to PGN was examined. In PGN-induced RAW264.7 cells, BAY11-7082, an inhibitor of NF-κB, inhibited iNOS by 37.65%, while 5AZ inhibited iNOS by 93.29% (Fig.3A). To confirm the effect of 5AZ on PGN-activated NF-κB, RAW264.7 cells were stimulated with PGN for 30 min., 4 hrs or 24 hrs. IκBα was degraded at 30 min. of PGN stimulation, and iNOS protein was increased significantly at 24 hrs (Fig.3B). This result suggested that the PGN-induced iNOS expression was mediated by NF-κB activation. To examine whether NF-κB activation events were inhibited by 5AZ, cells were stimulated with PGN with or without 5AZ for 30 min. Cytosolic IκBα degradation and nuclear translocation of p65, a subunit of NF-κB, were induced by PGN and were not influenced by 5AZ (Fig.3C).
Affiliation: Heart Research Center, Chonnam National University Hospital, Gwangju, South Korea.