CYTOMEGALOVIRUS REPLICATION IS NOT A CAUSE OF INSTABILITY IN UNSTABLEANGINA

Background Unstable angina is most frequently caused by coronary throm bosis, with or without plaque fissure, but the mechanisms underlying t hese events are still speculative. Since cytomegalovirus (CMV) antigen s and DNA encoding CMV major immediate-early (MIE) gene have been dete cted 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 unstab le angina. Methods and Results Twenty patients with unstable angina (1 2 men and 8 women; mean age, 62 years; range, 44 to 89 years) and 20 p atients with stable angina (16 men and 4 women; mean age, 62 years; ra nge, 43 to 81 years) who underwent successful directional coronary ath erectomy were enrolled in the study. The efficiency of mRNA extraction , transcription, and amplification from each coronary atherectomy spec imen 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 specim ens but one showed a positive hybridization signal. The negative sampl e was excluded from the study. Reverse transcription and thermal cycli ng amplification of a 145-bp CMV cDNA segment of the MIE gene were the n carried out. After Southern blotting and hybridization with a specif ic probe, none of the specimens showed a positive hybridization signal . Plasmid pACYC 184 containing the Xba I-inserted MIE gene cDNA was us ed as a positive control: as few as 10 molecules of the plasmid per re action were detectable after amplification. Conclusions Our results do not support the hypothesis that, in patients with unstable angina, re plication of CMV in coronary atherosclerotic plaques is a major cause of plaque instability. These findings suggest that the research for th e causes of unstable angina should be directed toward processes other than CMV replication.