Kloppenburg Geoffrey, de Graaf Rick, Herngreen Selma, Grauls Gert, Bruggeman Cathrien, Stassen Frank
Department of Medical Microbiology and Maastricht Infection Centre, University Hospital Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands.
Microbes Infect. 2005 Feb;7(2):164-70. doi: 10.1016/j.micinf.2004.10.008. Epub 2005 Jan 27.
Epidemiological and animal studies suggest a role for cytomegalovirus (CMV) in restenosis. Previously, we demonstrated that proliferating smooth muscle cells (SMCs) in the injured arterial wall are particularly susceptible to CMV-induced effects. Therefore, we hypothesised that, depending on the time point of infection after vascular injury, CMV infection may affect cell proliferation either in the media or in the neointima, thereby aggravating the process of restenosis. In the present study, we focused on the individual layers of the arterial wall by evaluating, besides the neointima-to-media ratio, the medial and neointimal area and cellularity in the rat femoral artery. Vascular injury was photochemically induced in rat femoral arteries. Immediately or 14 days thereafter, rats were infected with rat CMV (RCMV) or mock infected. The presence of RCMV in the vascular wall was determined at 3, 5, 14 and 35 days after infection by quantitative real-time PCR. When rats were infected immediately after injury, a significant increase was seen only in the medial but not in the neointimal cross-sectional area. On the other hand, when rats were infected 14 days after the initial injury, a significant increase was only seen in the neointimal area, thereby confirming our hypothesis that RCMV infection primary affects proliferating SMCs. As the mean number of SMCs per microm2 in both cell layers was unchanged despite an increase in cross-sectional area, this implies that RCMV stimulated SMC proliferation. Furthermore, these vascular effects were observed without the virus being abundantly present in the vascular wall, suggesting that inflammatory and immune-mediated responses to RCMV infection are more important in aggravating the response to vascular injury than the virus itself.
流行病学和动物研究表明巨细胞病毒（CMV）在再狭窄中起作用。此前，我们证明了受损动脉壁中增殖的平滑肌细胞（SMC）对CMV诱导的效应特别敏感。因此，我们推测，根据血管损伤后感染的时间点，CMV感染可能会影响中膜或内膜中的细胞增殖，从而加剧再狭窄过程。在本研究中，我们通过评估大鼠股动脉的内膜与中膜比值、中膜和内膜面积以及细胞密度，来关注动脉壁的各个层。在大鼠股动脉中通过光化学方法诱导血管损伤。损伤后立即或14天后，大鼠感染大鼠巨细胞病毒（RCMV）或进行假感染。通过定量实时PCR在感染后3、5、14和35天测定血管壁中RCMV的存在情况。当大鼠在损伤后立即感染时，仅中膜横截面积显著增加，而内膜未增加。另一方面，当大鼠在初次损伤后14天感染时，仅内膜面积显著增加，从而证实了我们的假设，即RCMV感染主要影响增殖的SMC。尽管横截面积增加，但两个细胞层中每平方微米SMC的平均数量未改变，这意味着RCMV刺激了SMC增殖。此外，可以观察到这些血管效应，而此时病毒在血管壁中并未大量存在，这表明对RCMV感染的炎症和免疫介导反应在加重对血管损伤的反应中比病毒本身更重要。
