Viral Agents and Systemic Levels of Inflammatory Cytokines in Vulnerable and Stable Atherosclerotic Carotid Plaques

Mazzaccaro D, Dolci M, Perego F, Delbue S, Giannetta M, Cardani R, Valentina Renna L, Costa E, Corsi-Romanelli MM, Galli C, Pariani E, Nano G, Clemente C, Basilico N. Viral Agents and Systemic Levels of Inflammatory Cytokines in Vulnerable and Stable Atherosclerotic Carotid Plaques. Ann Vasc Surg. 2022 May;82:325-333. doi: 10.1016/j.avsg.2021.10.070. Epub 2021 Dec 11. PMID: 34902464. Abstract <strong>Background: </strong>To investigate the presence of genetic material of viral agents and the serum level of inflammatory cytokines in patients submitted to carotid endarterectomy having vulnerable versus stable atherosclerotic plaques. <strong>Methods: </strong>Data of patients consecutively submitted to carotid endarterectomy for a significant stenosis from July 2019 to December 2019 were prospectively collected. The genetic material of Epstein-Barr (EBV), CitoMegalo (CMV), Herpes Simplex (HSV), Varicella-Zoster (VZV) and Influenza (IV) Viruses was searched in the patient's plaques, both in the "mid" of the plaque and in an adjacent lateral portion of no-plaque area. The serum levels of TNF-α, IL-1β, IL-6, IL10 and CCL5 were determined. The obtained results were then correlated to the histologic vulnerability of the removed carotid plaque. P values &lt; 0.05 were considered statistically significant. <strong>Results: </strong>Data of 50 patients were analyzed. A vulnerable plaque was found in 31 patients (62%). The genome of CMV, HSV, VZV and IV was not found in any of the vascular samples, while the EBV genome was found in the "mid" of 2 vulnerable plaques, but not in their respective control area. Eighty-two percent of patients who did not receive anti-IV vaccination (23/28) had vulnerable carotid plaque, compared with 36% of vaccinated patients (8/22, P = 0.001). Serum levels of TNF-α and IL-6 were higher in patients with a vulnerable plaque compared to patients with a stable plaque (73.6 ± 238.2 vs. 3.9 ± 13.1 pg/ml, P= 0.01, and 45.9 ± 103.6 vs. 10.1 ± 25.3 pg/ml, P= 0.01, respectively), independent of comorbidities, viral exposure or flu vaccination. <strong>Conclusions: </strong>The EBV genome was found in the "core" of 2 vulnerable carotid plaques, but not in their respective adjacent control. Influenza vaccination was associated with a lower incidence of carotid plaque vulnerability. Serum levels of TNF-α and IL-6 were higher in patients with a vulnerable plaque compared to patients with a stable plaque.Mazzaccaro D、Dolci M、Perego F、Delbue S、Giannetta M、Cardani R、Valentina Renna L、Costa E、Corsi-Romanelli MM、Galli C、Pariani E、Nano G、Clemente C、Basilico N. 脆弱与稳定动脉粥样硬化性颈动脉斑块中的病毒病原体及系统性炎症细胞因子水平. 《血管外科年鉴（Annals of Vascular Surgery）》. 2022年5月;82:325-333. DOI: 10.1016/j.avsg.2021.10.070. 2021年12月11日在线发表. PMID: 34902464. **背景**：本研究旨在探讨接受颈动脉内膜切除术（carotid endarterectomy）的患者中，动脉粥样硬化性颈动脉斑块为脆弱型与稳定型者的病毒病原体遗传物质存在情况，以及其血清炎症细胞因子（inflammatory cytokine）水平。**方法**：本研究前瞻性收集2019年7月至2019年12月期间，因显著颈动脉狭窄接受颈动脉内膜切除术的连续入组患者数据。在患者的斑块"中部"及相邻无斑块区域的侧部组织中，分别检测Epstein-Barr病毒（EB病毒，Epstein-Barr Virus, EBV）、巨细胞病毒（Cytomegalovirus, CMV）、单纯疱疹病毒（Herpes Simplex Virus, HSV）、水痘-带状疱疹病毒（Varicella-Zoster Virus, VZV）及流感病毒（Influenza Virus, IV）的遗传物质。同时检测患者血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）及趋化因子配体5（CCL5）的水平。将所得结果与切除的颈动脉斑块的组织学脆弱性进行关联分析，以P值<0.05为具有统计学显著性。**结果**：本研究共分析50例患者的数据。其中31例（62%）患者的颈动脉斑块为脆弱型。所有血管样本中均未检测到巨细胞病毒（CMV）、单纯疱疹病毒（HSV）、水痘-带状疱疹病毒（VZV）及流感病毒（IV）的基因组，而在2个脆弱型斑块的"中部"检测到EB病毒（EBV）基因组，但在其对应的对照区域未检测到。未接种流感疫苗（anti-IV vaccination）的患者中，82%（23/28）存在颈动脉斑块脆弱性，而接种疫苗的患者中这一比例为36%（8/22，P=0.001）。与稳定型斑块患者相比，脆弱型斑块患者的血清TNF-α和IL-6水平更高（分别为73.6±238.2 vs 3.9±13.1 pg/ml，P=0.01；45.9±103.6 vs 10.1±25.3 pg/ml，P=0.01），且该结果不受合并症、病毒暴露或流感疫苗接种的影响。**结论**：本研究在2个脆弱型颈动脉斑块的"核心"区域检测到EB病毒（EBV）基因组，但在其相邻的对照区域未检测到。流感疫苗接种与颈动脉斑块脆弱性的较低发生率相关。与稳定型斑块患者相比，脆弱型斑块患者的血清TNF-α和IL-6水平更高。