Role of smooth muscle cell death in advanced coronary primary lesions:: implications for plaque instability
Role of smooth muscle cell death in advanced coronary primary lesions:: implications for plaque instability
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DOI：
10.1016/s0008-6363(98)00318-6
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发表时间：
1999-02-01
影响因子：
10.8
通讯作者：
Lüderitz, B
中科院分区：
文献类型：
--
作者：
Bauriedel, G;Hutter, R;Lüderitz, B
目的：冠状动脉粥样硬化的不稳定性导致急性冠状动脉综合征的发生，包括心肌梗死和死亡，以及动脉硬化疾病的进展。到目前为止，导致斑块破裂的潜在因素和机制尚未完全了解。由于平滑肌细胞（SMCs）含量低显然起着关键作用，因此问题指向导致内膜SMCs丢失的事件。方法：我们比较了25例不稳定型心绞痛患者和25例稳定型心绞痛患者的冠状动脉粥样硬化切除术标本。透射电镜检测内膜细胞群，检测细胞凋亡的分期和类型，并区分凋亡和坏死。结果：与稳定型心绞痛斑块相比，不稳定型心绞痛斑块中巨噬细胞/淋巴细胞增多，SMCs明显减少（P=0.01）。所有冠状动脉粥样硬化均有特定的细胞死亡形式，细胞凋亡和坏死。作为关键发现，不稳定与稳定心绞痛病变中，SMCs发生凋亡的比例和凋亡的SMCs胞浆残留物（基质囊泡）的频率均显著增加（P=0.002和P=0.002）。第一次冠状动脉粥样硬化组细胞坏死发生率更高（P=0.02）。不稳定型心绞痛斑块中凋亡细胞频率与坏死细胞频率呈正相关（r=0.41， P=0.04），基质囊泡频率与坏死细胞频率呈正相关（r=0.63， P=0.001），而稳定型心绞痛斑块中凋亡细胞频率与坏死细胞频率呈正相关。结论：我们的数据表明，凋亡和坏死导致的高细胞死亡是与不稳定心绞痛相关的晚期冠状动脉原发病变的基本原位特征，这可能解释了其（可存活的）SMCs密度低的原因。因此，为了稳定冠状动脉粥样硬化的内膜斑块质地，防止斑块破裂，应考虑拮抗内膜细胞死亡。(C) 1999 Elsevier Science B.V.版权所有
Objective: Instability of coronary atheroma leads to the onset of acute coronary syndromes including myocardial infarction and death, as well as to the progression of the arteriosclerotic disease. As yet, the underlying factors and mechanisms causing plaque rupture are not completely understood. Since a low content of smooth muscle cells (SMCs) apparently plays a key role, the question points to the events leading to the loss of intimal SMCs. Methods: We compared coronary atherectomy specimens from 25 patients with unstable angina to those from 25 patients with stable angina. Transmission electron microscopy was used to identify intimal cell population, to detect stage and cell type of apoptosis, and to differentiate between apoptosis and necrosis. Results: plaques associated with unstable angina contained more macrophages/lymphocytes and significantly less SMCs (P=0.01), compared with stable angina plaques. Specific cell death forms, apoptosis and necrosis, were present in all coronary atheroma. As key findings, both the proportion of SMCs undergoing apoptosis and the frequency of cytoplasmic remnants of apoptotic SMCs (matrix vesicles) were significantly increased in unstable versus stable angina lesions (P=0.002 and P=0.002). In addition, cellular necrosis was more frequent in the first coronary atheroma group (P=0.02). Positive correlations were found between the frequency of apoptotic cells and necrosis (r=0.41, P=0.04), and that of matrix vesicles and necrosis (r=0.63, P=0.001) only in plaques with unstable angina, but not in those with stable angina. Conclusions: Our data demonstrate that high cell death due to apoptosis and necrosis is a basic in situ feature found in advanced coronary primary lesions associated with unstable angina, possibly explaining their low density of (viable) SMCs. Thus, antagonization of intimal cell death should be considered in order to stabilize the intimal plaque texture of coronary atheroma with the ultimate goal to prevent plaque rupture. (C) 1999 Elsevier Science B.V. All rights reserved.