Division of Infectious Disease, Department of Medicine (T.K., M.S., E.S.), David Geffen School of Medicine at UCLA.
Division of Cardiology, Department of Medicine (I.R., E.T., H.R.M.), David Geffen School of Medicine at UCLA.
Arterioscler Thromb Vasc Biol. 2023 Sep;43(9):1713-1718. doi: 10.1161/ATVBAHA.123.319172. Epub 2023 Jul 6.
Little is known whether electronic cigarettes (ECIG) increase vulnerability to future atherosclerotic cardiovascular disease. We determined, using an ex vivo mechanistic atherogenesis assay, whether proatherogenic changes including monocyte transendothelial migration and monocyte-derived foam cell formation are increased in people who use ECIGs.
In a cross-sectional single-center study using plasma and peripheral blood mononuclear cells from healthy participants who are nonsmokers or with exclusive use of ECIGs or tobacco cigarettes (TCIGs), autologous peripheral blood mononuclear cells with patient plasma and pooled peripheral blood mononuclear cells from healthy nonsmokers with patient plasma were utilized to dissect patient-specific ex vivo proatherogenic circulating factors present in plasma and cellular factors present in monocytes. Our main outcomes were monocyte transendothelial migration (% of blood monocyte cells that undergo transendothelial migration through a collagen gel) and monocyte-derived foam cell formation as determined by flow cytometry and the median fluorescence intensity of the lipid-staining fluorochrome BODIPY in monocytes of participants in the setting of an ex vivo model of atherogenesis.
Study participants (N=60) had median age of 24.0 years (interquartile range [IQR], 22.0-25.0 years), and 31 were females. Monocyte transendothelial migration was increased in people who exclusively used TCIGs (n=18; median [IQR], 2.30 [ 1.29-2.82]; <0.001) and in people who exclusively used ECIGs (n=21; median [IQR], 1.42 [ 0.96-1.91]; <0.01) compared with nonsmoking controls (n=21; median [IQR], 1.05 [0.66-1.24]). Monocyte-derived foam cell formation was increased in people who exclusively used TCIGs (median [IQR], 2.01 [ 1.59-2.49]; <0.001) and in people who exclusively used ECIGs (median [IQR], 1.54 [ 1.10-1.86]; <0.001) compared with nonsmoker controls (median [IQR], 0.97 [0.86-1.22]). Both monocyte transendothelial migration and monocyte-derived foam cell formation were higher in TCIG smokers compared with ECIG users and in ECIG users who were former smokers versus ECIG users who were never smokers (<0.05 for all comparisons).
The finding of alterations in proatherogenic properties of blood monocytes and plasma in TCIG smokers compared with nonsmokers validates this assay as a strong ex vivo mechanistic tool with which to measure proatherogenic changes in people who use ECIGs. Similar yet significantly less severe alterations in proatherogenic properties of monocytes and plasma were detected in the blood from ECIG users. Future studies are necessary to determine whether these findings are attributable to a residual effect of prior smoking or are a direct effect of current ECIG use.
目前尚不清楚电子烟是否会增加未来发生动脉粥样硬化性心血管疾病的易感性。我们通过体外动脉粥样硬化发生机制测定法来确定，使用电子烟（ECIG）的人群中是否会出现单核细胞跨内皮迁移和单核细胞源性泡沫细胞形成等促动脉粥样硬化变化增加。
在一项横断面单中心研究中，我们使用了来自健康非吸烟者或仅使用 ECIG 或烟草香烟（TCIG）者的血浆和外周血单核细胞，利用源自患者血浆的自体外周血单核细胞和源自健康非吸烟者血浆的混合外周血单核细胞，来分离存在于血浆中的患者特异性体外促动脉粥样硬化循环因子和存在于单核细胞中的细胞因子。我们的主要结局是通过流式细胞术测定单核细胞跨内皮迁移（通过胶原凝胶穿过的血液单核细胞的百分比）和单核细胞源性泡沫细胞形成，以及通过单核细胞中脂质染色荧光染料 BODIPY 的中荧光强度来确定。参与者处于体外动脉粥样发生模型中。
研究参与者（N=60）的中位年龄为 24.0 岁（四分位间距 [IQR]，22.0-25.0 岁），其中 31 名女性。仅使用 TCIG 的参与者（n=18；中位数 [IQR]，2.30 [1.29-2.82]；<0.001）和仅使用 ECIG 的参与者（n=21；中位数 [IQR]，1.42 [0.96-1.91]；<0.01）的单核细胞跨内皮迁移率高于不吸烟的对照组（n=21；中位数 [IQR]，1.05 [0.66-1.24]）。仅使用 TCIG 的参与者（中位数 [IQR]，2.01 [1.59-2.49]；<0.001）和仅使用 ECIG 的参与者（中位数 [IQR]，1.54 [1.10-1.86]；<0.001）的单核细胞源性泡沫细胞形成率高于不吸烟的对照组（中位数 [IQR]，0.97 [0.86-1.22]）。与 ECIG 使用者和 ECIG 使用者中的前吸烟者相比，TCIG 吸烟者的单核细胞跨内皮迁移和单核细胞源性泡沫细胞形成率更高（<0.05 用于所有比较）。
与不吸烟者相比，TCIG 吸烟者血液单核细胞和血浆促动脉粥样硬化特性的改变验证了该测定法作为一种强大的体外机制工具，可以用于测量使用 ECIG 者的促动脉粥样硬化变化。在 ECIG 使用者的血液中也检测到单核细胞和血浆促动脉粥样硬化特性的类似但明显程度较轻的改变。需要进一步的研究来确定这些发现是否归因于先前吸烟的残留影响，还是当前 ECIG 使用的直接影响。
