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.Ejection fraction (59.00 ± 8.03% versus 42.52 ± 2.58%), contractility (LV dP/dt-max, 8299.76 ± 411.56 mmHg versus 6610.36 ± 282.37 mmHg) and relaxation indices (LV dP/dt-min, -4661.37 ± 210.73 mmHg versus -4219.50 ± 162.98 mmHg) were improved after 5AZ administration.Cardiac fibrosis in the MI+5AZ was 8.14 ± 1.00%, compared with 14.93 ± 2.98% in the MI group (P < 0.05).
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.