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心血管代谢危险因素与人类免疫细胞线粒体呼吸有关。

Cardiometabolic risk factors are associated with immune cell mitochondrial respiration in humans.

机构信息

Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware.

出版信息

Am J Physiol Heart Circ Physiol. 2020 Aug 1;319(2):H481-H487. doi: 10.1152/ajpheart.00434.2020. Epub 2020 Jul 17.

Abstract

Modifiable cardiometabolic risk factors induce the release of proinflammatory cytokines and reactive oxygen species from circulating peripheral blood mononuclear cells (PBMCs), resulting in increased cardiovascular disease risk and compromised immune health. These changes may be driven by metabolic reprogramming of PBMCs, resulting in reduced mitochondrial respiration; however, this has not been fully tested. We aimed to determine the independent associations between cardiometabolic risk factors including BMI, blood pressure, fasting glucose, and plasma lipids with mitochondrial respiration in PBMCs isolated from generally healthy individuals ( = 21) across the adult lifespan (12 men/9 women; age, 56 ± 21 yr; age range, 22-78 yr; body mass index, 27.9 ± 5.7 kg/m; blood pressure, 123 ± 16/72 ± 10 mmHg; glucose, 90 ± 14 mg/dL; low-density lipoprotein cholesterol (LDL-C), 111 ± 22 mg/dL; and high-density lipoprotein cholesterol (HDL-C), 62 ± 16 mg/dL). PBMCs were isolated from whole blood by density-dependent centrifugation and used to assess mitochondrial function by respirometry. Primary outcomes included basal and maximal oxygen consumption rate (OCR), which were subsequently used to determine spare respiratory capacity and OCR metabolic potential. After we corrected for systolic blood pressure (SBP), diastolic blood pressure (DBP), and blood glucose, LDL-C was negatively associated with maximal respiration ( = -0.56, = 0.016), spare respiratory capacity ( = -0.58, = 0.012), and OCR metabolic potential ( = -0.71, = 0.0011). In addition, SBP was negatively associated with OCR metabolic potential ( = -0.62, = 0.0056) after we corrected for DBP, blood glucose, and LDL-C. These data suggest a link between blood cholesterol, SBP, and mitochondrial health that may provide insight into how cardiometabolic risk factors contribute to impaired immune cell function. Independent of other cardiometabolic risk factors, low-density lipoprotein cholesterol, and systolic blood pressure were found to be negatively associated with several parameters of mitochondrial respiration in peripheral blood mononuclear cells of healthy adults. These data suggest that low-density lipoprotein cholesterol and systolic blood pressure may induce metabolic reprogramming of immune cells, contributing to increased cardiovascular disease risk and impaired immune health.

摘要

可改变的心血管代谢风险因素会从循环外周血单个核细胞 (PBMC) 中释放促炎细胞因子和活性氧,从而增加心血管疾病风险并损害免疫健康。这些变化可能是由 PBMC 的代谢重编程引起的,导致线粒体呼吸减少;然而,这尚未得到充分验证。我们旨在确定心血管代谢风险因素(包括 BMI、血压、空腹血糖和血浆脂质)与一般健康个体(= 21)分离的 PBMC 中线粒体呼吸之间的独立关联,这些个体跨越成年期(12 名男性/9 名女性;年龄 56 ± 21 岁;年龄范围 22-78 岁;体重指数 27.9 ± 5.7 kg/m;血压 123 ± 16/72 ± 10 mmHg;血糖 90 ± 14 mg/dL;低密度脂蛋白胆固醇 (LDL-C) 111 ± 22 mg/dL;高密度脂蛋白胆固醇 (HDL-C) 62 ± 16 mg/dL)。通过密度依赖的离心法从全血中分离 PBMC,并通过呼吸计评估线粒体功能。主要结果包括基础和最大耗氧量 (OCR),随后用于确定剩余呼吸能力和 OCR 代谢潜能。在我们校正收缩压 (SBP)、舒张压 (DBP) 和血糖后,LDL-C 与最大呼吸呈负相关(= -0.56,= 0.016),剩余呼吸能力(= -0.58,= 0.012)和 OCR 代谢潜能(= -0.71,= 0.0011)。此外,在我们校正 DBP、血糖和 LDL-C 后,SBP 与 OCR 代谢潜能呈负相关(= -0.62,= 0.0056)。这些数据表明血液胆固醇、SBP 和线粒体健康之间存在联系,这可能为我们提供有关心血管代谢风险因素如何导致免疫细胞功能受损的见解。独立于其他心血管代谢风险因素,低密度脂蛋白胆固醇和收缩压与健康成年人外周血单个核细胞中线粒体呼吸的几个参数呈负相关。这些数据表明,低密度脂蛋白胆固醇和收缩压可能会诱导免疫细胞的代谢重编程,从而增加心血管疾病风险并损害免疫健康。

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