Increased apoptosis in remote non-infarcted myocardium in multivessel coronary disease.
BACKGROUND
Multivessel coronary disease after myocardial infarction is a major risk factor for unfavorable cardiac remodeling and death due to pump failure, but underlying pathophysiologic mechanisms are still uncompletely established. Post-infarction myocardial apoptosis has been recently implicated as a cause of ongoing cell loss leading to cardiac failure. Our aim was to assess the role of post-infarction myocardial apoptosis and pro-apoptotic factor expression in the non-infarcted remote myocardium of subjects with multivessel coronary disease.


METHODS
Twenty-one males dying after recent myocardial infarction with permanent occlusion of the infarct-related artery were selected at autopsy. Apoptosis was assessed at viable myocardial regions remote from infarction by co-staining for in situ end-labeling of DNA fragmentation and cleaved caspase-3. Expression of pro-apoptotic factor bax and hypoxia-induced factor-1alpha was evaluated by immunohistochemistry.


RESULTS
Subjects with multivessel disease (N=11) showed a significantly two-fold higher myocardial apoptosis in comparison to subjects with single vessel disease (N=10) (0.9% vs. 0.5%, p=0.013). Similarly, myocardial bax expression was increased in patients with multivessel disease (3.0% vs. 1.4%, p=0.029). Stratification for the number of diseased coronary vessels confirmed the association between extent of coronary disease and apoptotic rates (p=0.022). Even in subjects dying over 30 days after infarction multivessel disease remained predictive of enhanced myocardiocyte apoptosis at remote regions (p=0.033).


CONCLUSIONS
Post-infarction myocardial apoptosis and bax expression in remote left ventricular regions are significantly increased in male patients with multivessel coronary disease in comparison to those with isolated infarct-related artery occlusion. These findings suggest that apoptotic cell loss in the viable non-infarcted myocardium, possibly due ongoing ischemia, may play a relevant role in the unfavorable clinical course typical of multivessel disease after myocardial infarction.
Institute of Cardiology, Catholic University, Rome, Italy.
Giuseppe G L
GG
Biondi-Zoccai
Antonio
A
Abbate
Fortunata
F
Vasaturo
Susanna
S
Scarpa
Daniele
D
Santini
Antonio Maria
AM
Leone
Quintino
Q
Parisi
Fabio
F
De Giorgio
Rossana
R
Bussani
Furio
F
Silvestri
Feliciano
F
Baldi
Luigi M
LM
Biasucci
Alfonso
A
Baldi
D017209:Apoptosis; D001344:Autopsy; D003327:Coronary Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology*; D020257:Ventricular Remodeling