Kol A, Sperti G, Shani J, Schulhoff N, van de Greef W, Landini M P, La Placa M, Maseri A, Crea F
Institute of Cardiology, Policlinico A. Gemelli, Catholic University of Rome, Italy.
Circulation. 1995 Apr 1;91(7):1910-3. doi: 10.1161/01.cir.91.7.1910.
Unstable angina is most frequently caused by coronary thrombosis, with or without plaque fissure, but the mechanisms underlying these events are still speculative. Since cytomegalovirus (CMV) antigens and DNA encoding CMV major immediate-early (MIE) gene have been detected in atherosclerotic arterial walls, the active replication of CMV may be responsible for plaque instability. Therefore the expression of CMV MIE gene mRNA, an early marker of viral replication, was assessed in coronary atherectomy specimens from patients with stable or unstable angina.
Twenty patients with unstable angina (12 men and 8 women; mean age, 62 years; range, 44 to 89 years) and 20 patients with stable angina (16 men and 4 women; mean age, 62 years; range, 43 to 81 years) who underwent successful directional coronary atherectomy were enrolled in the study. The efficiency of mRNA extraction, transcription, and amplification from each coronary atherectomy specimen was assessed by performance of reverse transcription and thermal cycling amplification of a 548-bp human beta-actin cDNA segment. After Southern blotting and hybridization with a specific probe, all specimens but one showed a positive hybridization signal. The negative sample was excluded from the study. Reverse transcription and thermal cycling amplification of a 145-bp CMV cDNA segment of the MIE gene were then carried out. After Southern blotting and hybridization with a specific probe, none of the specimens showed a positive hybridization signal. Plasmid pACYC 184 containing the Xba I-inserted MIE gene cDNA was used as a positive control: as few as 10 molecules of the plasmid per reaction were detectable after amplification.
Our results do not support the hypothesis that, in patients with unstable angina, replication of CMV in coronary atherosclerotic plaques is a major cause of plaque instability. These findings suggest that the research for the causes of unstable angina should be directed toward processes other than CMV replication.
不稳定型心绞痛最常见的病因是冠状动脉血栓形成，伴或不伴有斑块破裂，但其潜在机制仍属推测。由于在动脉粥样硬化的动脉壁中已检测到巨细胞病毒（CMV）抗原及编码CMV主要立即早期（MIE）基因的DNA，因此CMV的活跃复制可能是斑块不稳定的原因。因此，在稳定型或不稳定型心绞痛患者的冠状动脉粥样斑块切除术标本中评估了作为病毒复制早期标志物的CMV MIE基因mRNA的表达。
本研究纳入了20例接受成功定向冠状动脉粥样斑块切除术的不稳定型心绞痛患者（12例男性，8例女性；平均年龄62岁；范围44至89岁）和20例稳定型心绞痛患者（16例男性，4例女性；平均年龄62岁；范围43至81岁）。通过对548bp人β-肌动蛋白cDNA片段进行逆转录和热循环扩增，评估了从每个冠状动脉粥样斑块切除术标本中提取、转录和扩增mRNA的效率。经过Southern印迹并用特异性探针杂交后，除1个标本外，所有标本均显示阳性杂交信号。该阴性样本被排除在研究之外。随后对MIE基因的145bp CMV cDNA片段进行逆转录和热循环扩增。经过Southern印迹并用特异性探针杂交后，所有标本均未显示阳性杂交信号。含有Xba I插入的MIE基因cDNA的质粒pACYC 184用作阳性对照：扩增后每个反应中低至10个质粒分子均可检测到。
我们的结果不支持以下假设，即在不稳定型心绞痛患者中，冠状动脉粥样硬化斑块中的CMV复制是斑块不稳定的主要原因。这些发现表明，对不稳定型心绞痛病因的研究应针对CMV复制以外的其他过程。
