Bauriedel G, Hutter R, Welsch U, Bach R, Sievert H, Lüderitz B
Department of Cardiology, University of Bonn, Germany.
Cardiovasc Res. 1999 Feb;41(2):480-8. doi: 10.1016/s0008-6363(98)00318-6.
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.
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.
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.
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.
冠状动脉粥样硬化斑块不稳定会导致包括心肌梗死和死亡在内的急性冠状动脉综合征的发作，以及动脉粥样硬化疾病的进展。迄今为止，导致斑块破裂的潜在因素和机制尚未完全明确。由于平滑肌细胞（SMC）含量低显然起着关键作用，问题指向导致内膜SMC丢失的相关事件。
我们将25例不稳定型心绞痛患者的冠状动脉斑块切除术标本与25例稳定型心绞痛患者的标本进行了比较。采用透射电子显微镜鉴定内膜细胞群，检测凋亡阶段和细胞类型，并区分凋亡与坏死。
与稳定型心绞痛斑块相比，不稳定型心绞痛相关斑块含有更多的巨噬细胞/淋巴细胞，且SMC明显更少（P = 0.01）。所有冠状动脉粥样斑块中均存在特定的细胞死亡形式，即凋亡和坏死。作为关键发现，与稳定型心绞痛病变相比，不稳定型心绞痛病变中发生凋亡的SMC比例以及凋亡SMC胞质残余物（基质小泡）的频率均显著增加（P = 0.002和P = 0.002）。此外，在第一组冠状动脉粥样斑块中细胞坏死更为常见（P = 0.02）。仅在不稳定型心绞痛斑块中发现凋亡细胞频率与坏死之间存在正相关（r = 0.41，P = 0.04），基质小泡频率与坏死之间存在正相关（r = 0.63，P = 0.001），而在稳定型心绞痛斑块中未发现。
我们的数据表明，凋亡和坏死导致的高细胞死亡率是与不稳定型心绞痛相关的晚期冠状动脉原发性病变的一种基本原位特征，这可能解释了其（存活）SMC密度较低的原因。因此，应考虑拮抗内膜细胞死亡，以稳定冠状动脉粥样斑块的内膜斑块结构，最终目的是预防斑块破裂。
