681 Cyclooxygenase-2 (COX-2) expression at site of recent myocardial infarction: friend or foe

Abstract

Background: Cyclo-oxygenase-2 (COX-2) is induced in cardiomyocytes only in response to stress, such as ischaemia. Objective: To assess COX-2 expression at the site of recent myocardial infarction. Methods: COX-2 expression was evaluated by specific immunostaining in cardiomyocytes from 23 subjects who died 10-60 days after acute myocardial infarction. The relation between COX-2 myocardial expression and apoptotic rate was investigated. Cardiomyocyte apoptotic rate was defined as the number of cells co-expressing in situ end labelling of DNA fragmentation (TUNEL) and immunostaining for activated caspase-3. Results: COX-2 expression was found in cardiomyocytes at the site of infarction in nine of 23 cases (39%). It was associated with fivefold higher apoptotic rates (median 17.9% (interquartile range 11.0-25.4%) v 3.7% (0.6-12.8%); p = 0.016), and apoptotic rate increased progressively from mild to intense COX-2 staining (p for trend 0.009). COX-2 expression co-localised with TUNEL nuclear staining in myocytes, and there was a high concordance between COX-2 and hypoxia induced factor 1-a staining (78%, p = 0.021) and between COX-2 and bax (83%, p = 0.014). Subjects showing myocardial COX-2 expression were more likely to have enlarged hearts (p = 0.050), and intense COX-2 staining was strictly associated with symptomatic heart failure (p = 0.035). Conclusions: COX-2 is expressed in cardiomyocytes in nearly 40% of cases at the site of recent acute myocardial infarction, even late after the index event. Its expression was associated with extremely high apoptotic rates. These findings suggest a potential cause-effect link between COX-2 expression and enhanced myocardial apoptosis in ischaemic cardiomyopathy.

Protective Effects of Parecoxib, a Cyclo-Oxygenase-2 Inhibitor, in Postinfarction Remodeling in the Rat

“…Yet, current and prior findings in AMI model point to a proapoptotic effect of COX-2 in the ischemic heart. 5,8,16 The mechanisms by which COX-2 inhibition prevents apoptosis in the heart are still uncharacterized. The effects may be PGE-2 mediated and similar to those observed in ischemic brain injury.…”

Cyclo-oxygenase-2 (COX-2) inhibition reduces apoptosis in acute myocardial infarction

“…4 The use of COX-2 inhibitors (along with all non-steroidal antiinflammatory drugs) has become off-limit for patients with or at risk for acute coronary syndromes. 7 The reason why COX-inhibition may favor atherothrombosis is yet completely clear.…”

“…Transverse sections of the median third of the left ventricle were taken and immediately fixed in paraformaldehyde as previously specified. 4,5 Infarct size was quantified as a percentage of the whole circumference. Specific staining for COX-2 was assessed using a primary antibody (goat polyclonal sc-1745, Santa Cruz Biotechnology, CA, US) at the dilution of 1:100.…”

“…The detailed protocol was published elsewhere. 4 The peri-infarct area was defined as the zone bordering the infarct where viable myocardium was prevalent and reparative fibrosis was only marginal. 6 The apoptotic rate (AR) was expressed as the number of apoptotic cardiomyocytes on all cardiomyocytes per field.…”

“…COX-2 expression in subjects with AMI was associated with significantly higher rates of cardiomyocyte apoptosis which may explain progressive cell loss and adverse remodeling. 4 Interestingly COX-2 expression was found in the very same cell undergoing DNA fragmentation 4 and death raising the issue whether COX-2 itself could be mediating the negative effects of ischemia by promoting apoptosis.…”