Sambiase N V, Higuchi M L, Nuovo G, Gutierrez P S, Fiorelli A I, Uip D E, Ramires J A
Laboratory of Pathology, University of São Paulo Medical School, Brazil.
Mod Pathol. 2000 Feb;13(2):173-9. doi: 10.1038/modpathol.3880032.
Accelerated graft coronary atherosclerosis is the main obstacle to long-term survival in patients who have had a heart transplant. A possible involvement of the human cytomegalovirus (HCMV) in this type of coronary atherosclerosis has been postulated by many authors but has not been definitively demonstrated. In an attempt to clarify the role of HCMV infection in the pathogenesis of this complication, we looked for in situ antigens or DNA of HCMV in 30 coronary artery segments obtained at necropsy from patients who had undergone orthotopic cardiac transplantation at the São Paulo Heart Institute. We tried to correlate these HCMV markers with the presence of inflammation and/or atherosclerosis in histologic sections. The patients were grouped as follows: GI, less than 170 days of graft survival and absent/mild atherosclerosis; GII, more than 170 days of graft survival and absent/mild atherosclerosis; GIII, more than 170 days of graft survival and severe/moderate atherosclerosis (170 days was the shortest graft survival time associated with atherosclerosis). The search for HCMV genome and antigens in the coronary artery sections was performed using immunohistochemistry, in situ hybridization, and polymerase chain reaction in situ techniques. Immunohistochemistry and in situ hybridization revealed no evidence of HCMV in all 30 cases. Polymerase chain reaction in situ revealed scarce HCMV-positive lymphocytes in two cases (one each from GI and GIII) located in the adventitial layer. These findings preclude a direct role for the HCMV in the pathogenesis of accelerated graft coronary atherosclerosis. However, the possibility of an indirect effect of the virus, such as an immune-mediated inflammatory response by the host that increases the expression of histocompatibility antigens, leading to tissue injury, cannot be excluded.
移植心脏冠状动脉粥样硬化加速是心脏移植患者长期生存的主要障碍。许多作者推测人类巨细胞病毒（HCMV）可能参与了这类冠状动脉粥样硬化，但尚未得到确切证实。为了阐明HCMV感染在这种并发症发病机制中的作用，我们在圣保罗心脏研究所对30例原位心脏移植患者尸检时获取的冠状动脉节段中寻找HCMV的原位抗原或DNA。我们试图将这些HCMV标志物与组织学切片中的炎症和/或动脉粥样硬化的存在情况相关联。患者分为以下几组：GI组，移植存活时间少于170天且无/轻度动脉粥样硬化；GII组，移植存活时间超过170天且无/轻度动脉粥样硬化；GIII组，移植存活时间超过170天且有重度/中度动脉粥样硬化（170天是与动脉粥样硬化相关的最短移植存活时间）。使用免疫组织化学、原位杂交和聚合酶链反应原位技术在冠状动脉切片中寻找HCMV基因组和抗原。免疫组织化学和原位杂交在所有30例病例中均未发现HCMV的证据。原位聚合酶链反应在两例病例（GI组和GIII组各1例）的外膜层发现了少量HCMV阳性淋巴细胞。这些发现排除了HCMV在移植心脏冠状动脉粥样硬化加速发病机制中的直接作用。然而，不能排除病毒的间接作用，例如宿主的免疫介导炎症反应增加组织相容性抗原的表达，导致组织损伤。
