We investigate the influence of
des-Aspartate-angiotensin-I (DAA-I) on the
cytokine expression profile in a rodent model of
myocardial infarction.
Myocardial infarction model was created in female Wistar rats by coronary artery
ligation. Animals were randomized to receive intravenously either a daily dose of 1.2 mug DAA-I/kg
body weight (group 1; n = 60) or saline (group 2; n = 60) for 14 days after
infarction. Heart function was assessed by echocardiography. Animals were euthanized at 1, 3, 7, 14 and 31 days. Morphometric analysis using tetrazolium
chloride staining revealed that
infarct size was reduced by 32.2% (p < 0.05) in group 1 after 14 days of DAA-I treatment. Left ventricular ejection fraction in group 1 improved significantly (73.4%) as compared to group 2 (47.7%; p < 0.001). Immunostaining for immune cells at the
infarct site showed that CD8+ lymphocytes infiltration at the
infarct site declined in group 1 (15 +/- 5 cells) as compared to group 2 (50 +/- 6 cells; p < 0.001). Infiltration of monocytes and macrophages remained high at day 14 in group 2 (126 +/- 40 cells) as compared to group 1 (49 +/- 11 cells; p = 0.006). Multiplex PCR was done for differential gene expression of various pro-inflammatory
cytokines.
IL-6,
TNF-alpha,
TGF-beta and
GM-CSF expression were significantly down-regulated in the
infarct, peri-
infarct and contra-lateral zones of the left ventricle in group 1 as compared to group 2.
IL-6,
TGF-beta and
GM-CSF expression started to decline from day 1 of DAA-I treatment while
TNF-alpha expression only reduced after 7 days of DAA-I treatment. We conclude that DAA-I prevented
infarct expansion through suppression of inflammatory
cytokines and immune cell infiltration in the
infarct region.