Biondi-Zoccai Giuseppe G L, Abbate Antonio, Vasaturo Fortunata, Scarpa Susanna, Santini Daniele, Leone Antonio Maria, Parisi Quintino, De Giorgio Fabio, Bussani Rossana, Silvestri Furio, Baldi Feliciano, Biasucci Luigi M, Baldi Alfonso
Institute of Cardiology, Catholic University, Rome, Italy.
Int J Cardiol. 2004 Mar;94(1):105-10. doi: 10.1016/j.ijcard.2003.07.001.
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.
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.
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).
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.
心肌梗死后多支冠状动脉疾病是心脏不良重塑和因泵衰竭导致死亡的主要危险因素，但其潜在的病理生理机制仍未完全明确。近期研究表明，梗死后心肌细胞凋亡是导致持续细胞丢失并引发心力衰竭的原因。我们的目的是评估多支冠状动脉疾病患者梗死灶远端非梗死心肌中梗死后心肌细胞凋亡及促凋亡因子表达的作用。
选取21例近期发生心肌梗死且梗死相关动脉永久性闭塞后死亡的男性患者进行尸检。通过DNA片段原位末端标记与裂解的半胱天冬酶-3共染色，评估远离梗死灶的存活心肌区域的细胞凋亡情况。采用免疫组织化学法评估促凋亡因子bax及缺氧诱导因子- $1\alpha$ 的表达。
与单支血管疾病患者（$N = 10$）相比，多支血管疾病患者（$N = 11$）的心肌细胞凋亡显著增加两倍（$0.9%$ 对 $0.5%$，$p = 0.013$）。同样，多支血管疾病患者的心肌bax表达也增加（$3.0%$ 对 $1.4%$，$p = 0.029$）。对病变冠状动脉血管数量进行分层分析证实了冠状动脉疾病程度与凋亡率之间的关联（$p = 0.022$）。即使在梗死30天后死亡的患者中，多支血管疾病仍然是远端区域心肌细胞凋亡增加的预测因素（$p = 0.033$）。
与单纯梗死相关动脉闭塞的男性患者相比，多支冠状动脉疾病男性患者梗死灶远端左心室区域的梗死后心肌细胞凋亡及bax表达显著增加。这些发现表明，存活的非梗死心肌中的凋亡细胞丢失，可能由于持续缺血，可能在心肌梗死后多支血管疾病典型的不良临床病程中起重要作用。
