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Increased apoptosis in remote non-infarcted myocardium in multivessel coronary disease
Giuseppe G L Biondi-Zoccai1, Antonio Abbate, Fortunata Vasaturo
1Institute of Cardiology, Catholic University, Rome, Italy.
Insights
Multivessel coronary disease after heart attack increases myocardial apoptosis (programmed cell death) in remote heart regions. This cell loss, potentially due to ongoing ischemia, contributes to poor outcomes in patients with multivessel coronary disease.
Area of Science:
- Cardiovascular pathology
- Myocardial infarction research
- Cellular apoptosis mechanisms
Background:
- Multivessel coronary disease (MVD) post-myocardial infarction (MI) is linked to adverse cardiac remodeling and mortality.
- Underlying mechanisms, particularly post-MI myocardial apoptosis, are not fully understood.
- Apoptosis in non-infarcted regions may contribute to ongoing cell loss and cardiac dysfunction.
Purpose of the Study:
- To investigate the role of post-infarction myocardial apoptosis in the remote myocardium of patients with MVD.
- To assess the expression of pro-apoptotic factors in relation to MVD after MI.
- To determine if MVD influences cell death in viable, non-infarcted heart tissue.
Main Methods:
- Autopsy study of 21 male patients with recent MI and occluded infarct-related artery.
- Apoptosis assessed via DNA fragmentation and cleaved caspase-3 staining in remote myocardium.
- Immunohistochemistry used to evaluate pro-apoptotic factor (Bax) and hypoxia-induced factor-1alpha expression.
Main Results:
- MVD patients (N=11) exhibited significantly higher myocardial apoptosis (0.9%) compared to single-vessel disease patients (N=10, 0.5%).
- Bax expression was also significantly increased in MVD patients (3.0%) versus single-vessel disease patients (1.4%).
- Apoptotic rates correlated with the extent of coronary artery disease and remained predictive of apoptosis even >30 days post-MI.
Conclusions:
- Post-infarction myocardial apoptosis and Bax expression are elevated in the remote myocardium of male patients with MVD.
- These findings suggest apoptotic cell loss in viable myocardium, possibly from ischemia, contributes to the poor prognosis in MVD post-MI.
- Targeting apoptosis may be a therapeutic strategy for patients with MVD after myocardial infarction.
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.
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