Reilly Nathalie A, Mulder Janneke W C M, Dekkers Koen F, Kuipers Thomas B, van Vark-van der Zee Leonie C, Mulder Monique T, Roeters van Lennep Jeanine E, Jukema J Wouter, Heijmans Bastiaan T
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Internal Medicine, Erasmus MC Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
JACC Basic Transl Sci. 2025 Aug 21;10(9):101359. doi: 10.1016/j.jacbts.2025.101359.
Triglycerides and T cells play a key role in atherosclerosis, the leading cause of cardiovascular disease (CVD). Moderately elevated triglycerides have emerged as a causal risk factor, and T cells are a prominent component of atherosclerotic plaques. This cross-sectional study examined transcriptomic differences in T cells among patients with varying triglyceride levels via RNA sequencing. We analyzed CD4 and CD8 T cells from 49 participants, including those with primary (genetic) and secondary moderate hypertriglyceridemia, severe hypertriglyceridemia, and hypotriglyceridemia. Patients with primary moderate hypertriglyceridemia exhibited a proinflammatory transcriptomic profile, including increased interleukin-6 receptor (IL6R) expression, which is implicated in CVD risk. Similar patterns appeared in CD8 T cells and, to a lesser extent, in secondary moderate hypertriglyceridemia patients. Conversely, transcriptomic differences were reversed in hypotriglyceridemia and absent in severe hypertriglyceridemia patients. These findings suggest that elevated triglycerides may contribute to CVD by promoting a proinflammatory transcriptomic profile in T cells.
甘油三酯和T细胞在动脉粥样硬化(心血管疾病的主要病因)中起关键作用。中度升高的甘油三酯已成为一种因果风险因素,而T细胞是动脉粥样硬化斑块的重要组成部分。这项横断面研究通过RNA测序检查了不同甘油三酯水平患者T细胞中的转录组差异。我们分析了49名参与者的CD4和CD8 T细胞,包括原发性(遗传性)和继发性中度高甘油三酯血症、重度高甘油三酯血症和低甘油三酯血症患者。原发性中度高甘油三酯血症患者表现出促炎转录组特征,包括白细胞介素-6受体(IL6R)表达增加,这与心血管疾病风险有关。类似模式也出现在CD8 T细胞中,在继发性中度高甘油三酯血症患者中程度较轻。相反,低甘油三酯血症患者的转录组差异则相反,重度高甘油三酯血症患者则不存在这种差异。这些发现表明,甘油三酯升高可能通过促进T细胞中的促炎转录组特征而导致心血管疾病。