Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom.
Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain.
Theranostics. 2021 Mar 31;11(12):5728-5741. doi: 10.7150/thno.58356. eCollection 2021.
Human Cytomegalovirus (CMV) infection is associated with atherosclerosis, higher cardiovascular disease (CVD) risk, and an increase in memory T-cells (T). T-cells have also been implicated in CVD, independently of CMV infection. To better understand the CMV-associated CVD risk, we examined the association between CMV (IgG) serostatus and central aortic (carotid-to-femoral) pulse wave velocity (cfPWV), an early, independent predictor of CVD. We also investigated if such an association might be reflected by the distribution of T and/or other T-cell subsets. Healthy older volunteers (60-93 years) underwent routine clinical and laboratory evaluation, including assessment of cfPWV in eligible participants. Flow-cytometry was used to assess proportions of memory T-cells, CD28 T-cells, and CMV-specific T-cells. The following associations were examined; CMV serostatus/cfPWV, CMV serostatus/proportion of T, proportion of T/cfPWV, CD28 T-cells/cfPWV, and CMV-specific T-cells/cfPWV. Linear regression models were used to adjust for age, sex, socioeconomic status, smoking, waist-to-hip ratio, cholesterol, and blood pressure as required. Statistically significant positive associations were found (P-values for the fully adjusted models are given); CMV serostatus/cfPWV in men (P ≤ 0.01) but not in women, CMV serostatus/proportions of CD4 T in men (P ≤ 0.05) but not in women; proportions of CD4 T/cfPWV among CMV seropositive (CMV+) people (P ≤ 0.05) but not CMV seronegative (CMV-) people. CMV infection increases the CVD risk of older men by increasing cfPWV. This may be mediated in part by increased proportions of CD4 T, higher numbers of which are found in CMV+ older people and more so among men than women. Given the high prevalence of CMV worldwide, our findings point to a significant global health issue. Novel strategies to mitigate the increased CVD risk associated with CMV may be required.
人类巨细胞病毒(CMV)感染与动脉粥样硬化、心血管疾病(CVD)风险增加以及记忆 T 细胞(T)增加有关。T 细胞也与 CVD 有关,与 CMV 感染无关。为了更好地了解 CMV 相关的 CVD 风险,我们研究了 CMV(IgG)血清状态与中心主动脉(颈动脉-股动脉)脉搏波速度(cfPWV)之间的关系,cfPWV 是 CVD 的早期独立预测指标。我们还研究了这种关联是否可以通过 T 细胞和/或其他 T 细胞亚群的分布来反映。健康的老年志愿者(60-93 岁)接受了常规的临床和实验室评估,包括对符合条件的参与者进行 cfPWV 评估。流式细胞术用于评估记忆 T 细胞、CD28 T 细胞和 CMV 特异性 T 细胞的比例。检查了以下关联;CMV 血清阳性状态/cfPWV、CMV 血清阳性状态/T 细胞比例、T 细胞比例/cfPWV、CD28 T 细胞/cfPWV 和 CMV 特异性 T 细胞/cfPWV。使用线性回归模型根据需要调整年龄、性别、社会经济地位、吸烟、腰臀比、胆固醇和血压。发现了具有统计学意义的正相关(完全调整模型的 P 值给出);男性 CMV 血清阳性状态/cfPWV(P≤0.01)但女性无此关联,男性 CMV 血清阳性状态/CD4 T 比例(P≤0.05)但女性无此关联;CMV 阳性(CMV+)人群中 CD4 T 细胞比例/cfPWV(P≤0.05)但 CMV 阴性(CMV-)人群中无此关联。CMV 感染通过增加 cfPWV 增加老年男性的 CVD 风险。这可能部分是通过增加 CD4 T 细胞的比例来介导的,CMV+老年人中 CD4 T 细胞的数量更高,男性比女性更多。鉴于 CMV 在全球的高流行率,我们的发现指出了一个重大的全球健康问题。可能需要采取新的策略来减轻与 CMV 相关的 CVD 风险增加。