Simões-Faria Rita, Daems Margo, Peacock Hanna M, Declercq Mathias, Willems Anton, Jones Elizabeth A V, Ghesquière Bart
Laboratory of Applied Mass Spectrometry, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Metabolomics Core Facility Leuven, Center for Cancer Biology, VIB, Leuven, Belgium.
Metabolomics. 2025 Jan 20;21(1):16. doi: 10.1007/s11306-024-02214-y.
Hemodynamic forces play a crucial role in modulating endothelial cell (EC) behavior, significantly influencing blood vessel responses. While traditional in vitro studies often explore ECs under static conditions, ECs are exposed to various hemodynamic forces in vivo. This study investigates how wall shear stress (WSS) influences EC metabolism, focusing on the interplay between WSS and key metabolic pathways.
The aim of this study is to examine the effects of WSS on EC metabolism, specifically evaluating its impact on central carbon metabolism and glycolysis using transcriptomics and tracer metabolomics approaches.
ECs were exposed to WSS, and transcriptomic analysis was performed to assess gene expression changes related to metabolic pathways. Tracer metabolomics was used to track metabolic fluxes, focusing on glutamine and glycolytic metabolism. Additionally, chemical inhibition of glutamate dehydrogenase was conducted to evaluate its role in EC fitness under WSS.
Transcriptomic data revealed upregulation of glutamine and glutamate pathways, alongside downregulation of glycolytic activity in ECs exposed to WSS. Tracer metabolomics confirmed that WSS promotes glutamine anaplerosis into the Krebs cycle, while decreasing glycolytic metabolism. Suppression of glutamate dehydrogenase impaired EC fitness under WSS conditions.
Our findings illuminate that ECs subjected to WSS exhibit a preference for glutamine as a key nutrient source for central carbon metabolism pathways, indicating diminished reliance on glycolysis. This study elucidates the nutritional predilections and regulatory mechanisms governing EC metabolism under WSS in vitro, underscoring the pivotal role of physical stimuli in shaping EC metabolic responses.
血流动力学力在调节内皮细胞（EC）行为中起着关键作用，对血管反应有显著影响。虽然传统的体外研究通常在静态条件下探索内皮细胞，但内皮细胞在体内会受到各种血流动力学力的作用。本研究调查壁面剪应力（WSS）如何影响内皮细胞代谢，重点关注WSS与关键代谢途径之间的相互作用。
本研究的目的是检查WSS对内皮细胞代谢的影响，具体使用转录组学和示踪代谢组学方法评估其对中心碳代谢和糖酵解的影响。
将内皮细胞暴露于WSS，并进行转录组分析以评估与代谢途径相关的基因表达变化。示踪代谢组学用于追踪代谢通量，重点关注谷氨酰胺和糖酵解代谢。此外，进行谷氨酸脱氢酶的化学抑制以评估其在WSS条件下对内皮细胞健康的作用。
转录组数据显示，暴露于WSS的内皮细胞中谷氨酰胺和谷氨酸途径上调，同时糖酵解活性下调。示踪代谢组学证实，WSS促进谷氨酰胺补充进入三羧酸循环，同时降低糖酵解代谢。在WSS条件下，谷氨酸脱氢酶的抑制损害了内皮细胞的健康。
我们的研究结果表明，受到WSS作用的内皮细胞表现出对谷氨酰胺作为中心碳代谢途径关键营养源的偏好，表明对糖酵解的依赖性降低。本研究阐明了体外WSS条件下内皮细胞代谢的营养偏好和调节机制，强调了物理刺激在塑造内皮细胞代谢反应中的关键作用。
