Apoptosis predominates in nonmyocytes in heart failure
Apoptosis predominates in nonmyocytes in heart failure
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DOI：
10.1152/ajpheart.00310.2009
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发表时间：
2009-08-01
影响因子：
4.8
通讯作者：
Vatner, Stephen F.
中科院分区：
文献类型：
--
作者：
Park, Misun;Shen, You-Tang;Vatner, Stephen F.
Park M，Shen YT，Gaussin V，Heyndrickx GR，Bartunek J，Resuello RR，Natividad FF，Kitsis RN，Vatner DE，Vatner SF.心力衰竭时细胞凋亡主要发生在非心肌细胞。Am J Physiol Heart Circ Physiol 297：H785-H791，2009。首次发表于2009年5月22日; doi：10.1152/ajpheart.00310.2009。本研究的目的是确定灵长类动物和心力衰竭（HF）患者心肌细胞和非心肌细胞凋亡的分布。几乎所有的临床心脏病学家和心血管研究者都认为，心肌细胞凋亡被认为是HF的主要标志，是其发病机制中的主要因素。然而，由于心脏中75%的细胞是非肌细胞，因此确定HF中的细胞凋亡是发生在肌细胞还是非肌细胞中是很重要的。我们研究了非人灵长类动物慢性HF模型，在心肌梗死（MI）后2-6个月通过快速起搏诱导，以及缺血性心肌病患者的活检。用心肌标记物的双重标记来区分心肌细胞与非心肌细胞的凋亡。MI后左室射血分数下降（78%~ 60%），HF后左室射血分数进一步下降（35%，P < 0.05）。正如预期的那样，心肌梗死恢复后，心肌细胞凋亡总数增加（0.62个细胞/mm 2），并随着HF的发展进一步增加（1.91个细胞/mm 2）。令人惊讶的是，在MI和MI + HF中，以及在邻近和远端区域中，大多数凋亡细胞是非肌细胞。这也在缺血性心肌病患者的心肌活检中观察到。我们发现巨噬细胞占凋亡非肌细胞的最大比例（41%对18%中性粒细胞，16%成纤维细胞，25%内皮细胞和其他细胞）。尽管心力衰竭的人和猴心脏的特点是显著的细胞凋亡，与目前的概念相反，非心肌细胞的细胞凋亡是心肌细胞的8 - 9倍。
Park M, Shen YT, Gaussin V, Heyndrickx GR, Bartunek J, Resuello RR, Natividad FF, Kitsis RN, Vatner DE, Vatner SF. Apoptosis predominates in nonmyocytes in heart failure. Am J Physiol Heart Circ Physiol 297: H785-H791, 2009. First published May 22, 2009; doi: 10.1152/ajpheart.00310.2009.-The goal of this investigation was to determine the distribution of myocardial apoptosis in myocytes and nonmyocytes in primates and patients with heart failure (HF). Almost all clinical cardiologists and cardiovascular investigators believe that myocyte apoptosis is considered to be a cardinal sign of HF and a major factor in its pathogenesis. However, with the knowledge that 75% of the number of cells in the heart are nonmyocytes, it is important to determine whether the apoptosis in HF is occurring in myocytes or in nonmyocytes. We studied both a nonhuman primate model of chronic HF, induced by rapid pacing 2-6 mo after myocardial infarction (MI), and biopsies from patients with ischemic cardiomyopathy. Dual labeling with a cardiac muscle marker was used to discriminate apoptosis in myocytes versus nonmyocytes. Left ventricular ejection fraction decreased following MI (from 78% to 60%) and further with HF (35%, P < 0.05). As expected, total apoptosis was increased in the myocardium following recovery from MI (0.62 cells/mm(2)) and increased further with the development of HF (1.91 cells/mm(2)). Surprisingly, the majority of apoptotic cells in MI and MI + HF, and in both the adjacent and remote areas, were nonmyocytes. This was also observed in myocardial biopsies from patients with ischemic cardiomyopathy. We found that macrophages contributed the largest fraction of apoptotic nonmyocytes (41% vs. 18% neutrophils, 16% fibroblast, and 25% endothelial and other cells). Although HF in the failing human and monkey heart is characterized by significant apoptosis, in contrast to current concepts, the apoptosis in nonmyocytes was eight- to ninefold greater than in myocytes.