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: Inducible nitric oxide synthase was used as a marker of macrophages with the M1 phenotype. Inducible nitric oxide synthase mRNA expression reached its peak at 24 hrs after PGN treatment (Fig.1A). RAW264.7 macrophages were stimulated with PGN (10 μg/ml) with or without 5AZ (10 μM) for 24 hrs and culture media were collected to measure nitrite formation. 5-azacytidine treatment attenuated PGN-induced nitric oxide production to 22.13% (Fig.1B). In cells treated with PGN for various time intervals, it was found that the inhibition of nitrite formation by 5AZ was apparent between 8 and 24 hrs after PGN stimulation (Fig.1C). This finding indicated that 5AZ might not be involved in a rapid reaction such as NF-κB in response to PGN. The inhibitory effect of 5AZ on PGN-induced iNOS expression was also apparent at 24 hrs after PGN stimulation (Fig.1D). To determine which enzyme was responsible for nitrite formation in response to PGN, expression of iNOS and eNOS was determined by Western blot. eNOS was not induced by PGN in RAW264.7 macrophages, whereas iNOS was shown to be the principal enzyme for nitrite formation in RAW264.7 cells (Fig.1D).
Affiliation: Heart Research Center, Chonnam National University Hospital, Gwangju, South Korea.