Apoptosis and post-infarction left ventricular remodeling.
Apoptosis is a common pathological feature in acute myocardial infarction (AMI), however, its role in the later phases (>10 days) of AMI and in post-infarction left ventricular remodeling has not been characterized. The aim of the study was to identify signs of ongoing cell apoptosis late post AMI. Sixteen hearts were collected at autopsy from subjects 12 to 62 days after the onset of AMI. In situ end-labeling of DNA fragmentation (TUNEL) and co-staining with caspase-3 were performed. Double-positive cells were defined as apoptotic and the apoptotic rate was calculated. Values are expressed as median and interquartile range. Co-stainings with muscle-actin, splicing factor (SC35), PCNA, bax and bcl-2 were also performed. Apoptotic rates at site of infarction [25.4% (17.0-28.4%)] were significantly higher v those at remote regions [0.7% (0.5-0.8%) P<0.001] and significantly correlated to left ventricular longitudinal and transverse diameters [ r = +0.70 (P=0.016) and r = +0.63 (P=0.004) respectively]. Moreover, in subjects with persistently occluded infarct-related artery (14 cases) there was a significantly higher apoptotic rate at the site of infarction compared to those (2 cases) with patent artery [26.0% (21.9-28.5%) v 4.5% (0.6% and 8,4%);P=0.033]. A significantly greater bax immuno-reactivity close to the infarction v remote areas was found (P<0.001). High grade apoptosis is present at sites of infarction in the later phases post AMI. This is more evident if the infarct-related artery is persistently occluded and signs of ventricular remodeling are present. These data may provide an explanation of progressive late left ventricular dysfunction.
Baldi
Alfonso
A
Department of Biochemistry and Biophysics, F. Cedrangolo, Section of Anatomy, Second University of Naples, Italy. alfonsobaldi@tiscalinet.it
Abbate
Antonio
A
Bussani
Rossana
R
Patti
Giuseppe
G
Melfi
Rosetta
R
Angelini
Anna
A
Dobrina
Aldo
A
Rossiello
Raffaele
R
Silvestri
Furio
F
Baldi
Feliciano
F
Di Sciascio
Germano
G
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D012189:Retrospective Studies; D020257:Ventricular Remodeling / Q000502:physiology*