Apoptosis in the failing human heart
Apoptosis in the failing human heart
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DOI：
10.1056/nejm199704173361603
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发表时间：
1997-04-17
影响因子：
158.5
通讯作者：
Anversa, P
中科院分区：
文献类型：
--
作者：
Olivetti, G;Abbi, R;Anversa, P
背景心肌细胞丢失是缺血性或非缺血性心力衰竭发生的重要机制。然而，程序性细胞死亡（凋亡）是否涉及心力衰竭的终末期尚不清楚。因此，我们研究了难治性充血性heartfail.Methods患者心肌细胞凋亡的幅度从心脏的36例接受心脏移植和3例心肌梗死后不久死亡的患者的心脏。11例正常心脏标本作为对照。细胞凋亡进行了评价组织化学，生物化学，并结合组织化学分析和共聚焦显微镜。两个原癌基因的表达，影响细胞凋亡，BCL 2和BAX，也determined.Results心力衰竭的特点是由一个232倍的增加，心肌细胞凋亡和生化DNA梯状（凋亡的指标）的形态。肌细胞核中DNA链断裂的组织化学证明与共聚焦显微镜下染色质凝聚和断裂的记录相结合。所有这些结果反映了心肌细胞的凋亡。在心力衰竭患者的心脏中，标记有BCL 2（保护细胞免于凋亡）的心肌细胞的百分比是正常心脏的1.8倍，而标记有BAX（促进凋亡）的心肌细胞的百分比保持不变。结论在失代偿的人心脏中，尽管BCL 2的表达增强，但仍存在心肌细胞的程序性死亡，这一现象可能与心功能不全的进展有关。(C)1997年，马萨诸塞州医学会。
Background Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure.Methods Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined.Results Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. Ail these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting.Conclusions Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2 this phenomenon may contribute to the progression of cardiac dysfunction. (C) 1997, Massachusetts Medical Society.