Cardioprotective effect of des-Aspartate-angiotensin-I (DAA-I) on cytokine gene expression profile in ligation model of myocardial infarction.

Abstract

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.

• Authors: Abd Jalil Rufaihah, Husnain Kh Haider, Kwoon M Sim, Ping Z Ding, LiLi Beth Ramos, Shujia Jiang, Eugene K W Sim
• Journal: Life sciences (Life Sci) Vol. 78 Issue 12 Pg. 1341-51 (Feb 16 2006) ISSN: 0024-3205 [Print] Netherlands
• PMID: 16423369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Cytokines
• DNA Primers
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• Granulocyte-Macrophage Colony-Stimulating Factor
• Angiotensin I

Topics

• Angiotensin I (pharmacology)
• Animals
• Cardiotonic Agents (pharmacology)
• Cytokines (genetics)
• DNA Primers
• Disease Models, Animal
• Echocardiography
• Female
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics)
• Inflammation (genetics)
• Myocardial Infarction (drug therapy)
• Rats
• Rats, Wistar
• Transforming Growth Factor beta (genetics)
• Tumor Necrosis Factor-alpha (genetics)