In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 18, No. 6 ( 2014-06), p. 1018-1027
Abstract:
We examined whether a shift in macrophage phenotype could be therapeutic for myocardial infarction ( MI ). The mouse macrophage cell line RAW 264.7 was stimulated with peptidoglycan ( PGN ), with or without 5‐azacytidine (5 AZ ) treatment. MI was induced by ligation of the left anterior descending coronary artery in rats, and the rats were divided into two groups; a saline‐injection group and a 5 AZ ‐injection group (2.5 mg/kg/day, intraperitoneal injection). LV function was evaluated and immunohistochemical analyses were performed 2 weeks after MI . Cardiac fibrosis was induced by angiotensin II (AngII) infusion with or without 5 AZ (5 mg/kg/day) in mice. Nitric oxide was produced by PGN , which was reduced by 77.87% after 5 AZ treatment. Both induction of inducible nitric oxide synthase (i NOS ) and i NOS promoter activity by PGN were inhibited by 5 AZ . 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 5 AZ administration. Cardiac fibrosis in the MI +5 AZ was 8.14 ± 1.00%, compared with 14.93 ± 2.98% in the MI group ( P 〈 0.05). Arginase‐1(+) CD 68(+) macrophages with anti‐inflammatory phenotype were predominant in the infarct border zone of the MI +5 AZ group, in comparison with the MI group. AngII‐induced cardiac fibrosis was also attenuated after 5 AZ administration. In cardiac fibroblasts, pro‐fibrotic mediators and cell proliferation were increased by AngII, and these increases were attenuated after 5 AZ treatment. 5 AZ exerts its cardiac protective role through modulation of macrophages and cardiac fibroblasts.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2014.18.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2076114-4
Permalink