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Effects of aprotinin on gene expression and protein synthesis after ischemia and reperfusion in rats.
- Source :
-
Circulation [Circulation] 2007 Sep 11; Vol. 116 (11 Suppl), pp. I121-6. - Publication Year :
- 2007
-
Abstract
- Background: Reperfusion injury of ischemic myocardium has been attributed to neutrophil infiltration, inflammatory activation and cardiac necrosis/apoptosis. Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown.<br />Methods and Results: We studied aprotinin in a rat model of myocardial ischemia for 20 minutes and reperfusion for 20 minutes, 8 hours or 24 hours. Aprotinin (20,000 IU/kg) given 5 minutes before reperfusion significantly reduced leukocyte accumulation (P<0.01), myocardial injury (determined by CK depletion, P<0.01) and myocyte apoptosis (P<0.05) compared with vehicle treated rats. Differential gene expression analysis showed myocardial ischemia plus reperfusion increased expression of proinflammatory genes like P-selectin, E-selectin, intercellular adhesion molecule, tumor necrosis factor-alpha, tumor necrosis factor-alpha receptor, interleukin-6, monocyte chemoattractant protein-1, p53, and Fas (CD59). Aprotinin before reperfusion suppressed expression of these inflammatory genes. Finally, differential protein expression analysis demonstrated increased intercellular adhesion molecule-1, tumor necrosis factor-alpha, and p53 after myocardial ischemia plus reperfusion, and this effect was diminished by aprotinin.<br />Conclusions: We demonstrated myocardial ischemia plus reperfusion induced leukocyte accumulation, inflammation, gene expression, protein expression and finally tissue injury and showed aprotinin limiting reperfusion injury through each of these stages, even after 24 hours of reperfusion. This effect seems partly attributable to suppression of proinflammatory genes and leukocyte accumulation. This work casts further light on the complex signaling of ischemia and reperfusion.
- Subjects :
- Animals
Aprotinin pharmacology
Gene Expression Regulation drug effects
Myocardial Ischemia drug therapy
Myocardial Reperfusion methods
Myocardial Reperfusion Injury prevention & control
Protein Biosynthesis drug effects
Rats
Aprotinin therapeutic use
Gene Expression Regulation physiology
Myocardial Ischemia metabolism
Myocardial Reperfusion Injury metabolism
Protein Biosynthesis physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 116
- Issue :
- 11 Suppl
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 17846291
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.106.680249