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Apoptosis and post-infarction left ventricular remodeling
Alfonso Baldi1, Antonio Abbate, Rossana Bussani
1Department of Biochemistry and Biophysics, F. Cedrangolo, Section of Anatomy, Second University of Naples, Italy. alfonsobaldi@tiscalinet.it
Insights
Ongoing cell apoptosis occurs late after acute myocardial infarction (AMI), especially with artery occlusion. This late apoptosis correlates with left ventricular remodeling and dysfunction.
Area of Science:
- Cardiovascular Pathology
- Cellular Biology
Background:
- Apoptosis is a known feature of acute myocardial infarction (AMI).
- The role of apoptosis in later stages (>10 days) post-AMI and its impact on left ventricular remodeling remain unclear.
Purpose of the Study:
- To investigate the presence and extent of ongoing apoptosis in the late phases following acute myocardial infarction.
- To correlate late apoptotic rates with left ventricular remodeling and infarct-related artery status.
Main Methods:
- Autopsy hearts from 16 subjects 12-62 days post-AMI were analyzed.
- In situ end-labeling (TUNEL) and co-staining with caspase-3 identified apoptotic cells.
- Immunohistochemistry for muscle-actin, SC35, PCNA, bax, and bcl-2 was performed.
Main Results:
- Significantly higher apoptotic rates were observed at infarct sites (25.4%) compared to remote regions (0.7%) (P<0.001).
- Apoptotic rates correlated with left ventricular dimensions (longitudinal r=+0.70, transverse r=+0.63).
- Higher apoptosis rates were found in persistently occluded infarct-related arteries (26.0%) versus patent arteries (4.5%) (P=0.033).
Conclusions:
- High-grade apoptosis persists late post-AMI, particularly at infarct sites.
- Persistent artery occlusion and ventricular remodeling are associated with increased late apoptosis.
- These findings may explain progressive left ventricular dysfunction after AMI.
Abstract:
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.