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Pretreament with losartan affects the inflammation following cardiac injury
Author(s) -
Le Saux Claude Jourdan,
Miyasato Shelley,
Rueli Rachel
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.644.4
Subject(s) - losartan , inflammation , fibrosis , angiotensin ii , medicine , endocrinology , ventricular remodeling , receptor , heart failure
Activation of the local renin‐angiotensin system (RAS) following cardiac injury participates in remodeling process. We hypothesized that mice treated with losartan, an angiotensin II receptor blocker, will prevent TGF‐b signaling activation leading to attenuated remodeling. C57BL/6J mice, 8–10 weeks old underwent cryoablasion of the left ventricle. At day 21 mice received losartan (0.6g/l) in their drinking water until sacrificed. Heart tissue was collected at several time points. The inflammatory response was determined by characterization of immune cell infiltration and cytokine mRNA abundance. Cardiac remodeling was assessed by extracellular matrix gene expression and quantification of collagen deposition by picrosirius red stain. TGF‐b signaling activation was determined by western blot analysis. All mice showed a peak of inflammation at day 3, and resolution by day 14. Pretreatment with losartan significantly increased macrophage infiltration. It significantly increased TNF‐a; mRNA at days 3 and 14. The level of TGF‐b mRNA was not affected by losartan, and none of the TGF‐b signaling pathways were activated. Correspondingly, collagen deposition did not significantly change. In contrast to other studies where losartan was given at the onset of injury, treatment prior to induction of cardiac injury may enhance inflammation, while modestly attenuating fibrosis. Grant Funding Source : NIH‐NCRR RR016453 , Hawaii Community Foundation 20080485