Abusheikha Aya Jamal, Johnson Corbin S C, Snyder-Mackler Noah, Zimmerman Kip D, Negrey Jacob D, Chiou Kenneth L, Frye Brett M, Howard Timothy D, Shively Carol A, Register Thomas C
Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
Department of Neurology, University of Washington, Seattle, WA, United States.
Front Nutr. 2025 Jul 10;12:1564741. doi: 10.3389/fnut.2025.1564741. eCollection 2025.
Western diets and social subordination are associated with increased risk of cardiovascular disease. In this study, we investigated the impact of Western versus Mediterranean diets and social status on atherogenesis and arterial transcriptional profiles in a 30-month randomized study in middle-aged, cynomolgus monkeys (). Atherosclerosis (intimal area) in the left anterior descending (LAD) coronary artery was higher in the Western diet group compared to the Mediterranean diet group ( = 5.25, = 0.03). There was no effect of diet on intimal lesion size in the iliac and carotid arteries ( > 0.05). Diet altered the transcriptome in iliac arteries; at an FDR threshold of 0.05, seven transcripts were upregulated (, and ENSMFAG00000052859), and 13 transcripts were downregulated (, , and ) in the Western compared to the Mediterranean diet cohort. These genes are associated with endothelial dysfunction, smooth muscle proliferation and migration, angiogenesis, and abnormal extracellular matrix (ECM) dynamics. In addition, two transcripts (ENSMFAG00000064154 [LncRNA] and ENSMFAG00000057515 [small nucleolar RNA U13]) were downregulated in subordinate monkeys relative to their dominant counterparts (FDR < 0.05). There was no effect of diet on the carotid artery transcriptome, but we did identify significant social status effects: Eleven transcripts were upregulated (, KCNIP3, ENSMFAG00000059809 [LncRNA], and ENSMFAG00000053865 [secreted protein A0A7N9CS45]), and seven transcripts were downregulated (, and ENSMFAG00000050714 [LncRNA]) in subordinate relative to dominant monkeys. These alterations were associated with dysregulated vascular tone and smooth muscle contractility, apoptosis, and abnormal ECM dynamics. These findings demonstrate differential effects of diet composition and social status depending on arterial sites. The effects of Western diet were observed primarily in the coronary and iliac arteries, whereas social status differences were observed primarily in the carotid arteries. Our results demonstrate that Western diets and social subordination have adverse, yet distinct and tissue-specific impacts on arterial atherogenesis and transcriptional profiles, highlighting the interplay between diet, social hierarchy, and vascular health.
西方饮食和社会从属地位与心血管疾病风险增加有关。在本研究中，我们在一项针对中年食蟹猴的为期30个月的随机研究中，调查了西方饮食与地中海饮食以及社会地位对动脉粥样硬化形成和动脉转录谱的影响。与地中海饮食组相比，西方饮食组左前降支（LAD）冠状动脉的动脉粥样硬化（内膜面积）更高（=5.25，=0.03）。饮食对髂动脉和颈动脉的内膜病变大小没有影响（>0.05）。饮食改变了髂动脉的转录组；在错误发现率（FDR）阈值为0.05时，与地中海饮食队列相比，西方饮食队列中有7个转录本上调（、和ENSMFAG00000052859），13个转录本下调（、和）。这些基因与内皮功能障碍、平滑肌增殖和迁移、血管生成以及细胞外基质（ECM）异常动态变化有关。此外，与优势猴相比，从属猴中有两个转录本（ENSMFAG00000064154 [长链非编码RNA]和ENSMFAG00000057515 [小核仁RNA U13]）下调（FDR<0.05）。饮食对颈动脉转录组没有影响，但我们确实发现了显著的社会地位效应：与优势猴相比，从属猴中有11个转录本上调（、KCNIP3、ENSMFAG00000059809 [长链非编码RNA]和ENSMFAG00000053865 [分泌蛋白A0A7N9CS45]），7个转录本下调（和ENSMFAG00000050714 [长链非编码RNA]）。这些改变与血管张力失调、平滑肌收缩性、细胞凋亡以及ECM异常动态变化有关。这些发现表明，饮食组成和社会地位的影响因动脉部位而异。西方饮食的影响主要在冠状动脉和髂动脉中观察到，而社会地位差异主要在颈动脉中观察到。我们的结果表明，西方饮食和社会从属地位对动脉粥样硬化形成和转录谱有不良影响，但具有明显的组织特异性，突出了饮食、社会等级制度和血管健康之间的相互作用。
