Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe?
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-alpha 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.
Abbate
A
A
Institute of Cardiology, Catholic University, Rome, Italy. abbatea@yahoo.com
Santini
D
D
Biondi-Zoccai
G G L
GG
Scarpa
S
S
Vasaturo
F
F
Liuzzo
G
G
Bussani
R
R
Silvestri
F
F
Baldi
F
F
Crea
F
F
Biasucci
L M
LM
Baldi
A
A
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D015415:Biomarkers; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases