Wall shear stress modulates metabolic pathways in endothelial cells

Area of Science:

• Cellular Metabolism
• Biophysics
• Vascular Biology

Background:

• Endothelial cells (ECs) are constantly exposed to hemodynamic forces in vivo, unlike static in vitro models.
• Wall shear stress (WSS) significantly influences EC behavior and blood vessel responses.
• Understanding EC metabolic adaptation to WSS is crucial for vascular health.

Purpose of the Study:

• To investigate the impact of WSS on EC metabolism, focusing on central carbon metabolism and glycolysis.
• To elucidate the interplay between WSS and key metabolic pathways in ECs.
• To evaluate the role of glutamine and glycolysis in ECs under WSS.

Main Methods:

• ECs were subjected to WSS in vitro.
• Transcriptomic analysis was performed to identify changes in metabolic gene expression.
• Tracer metabolomics tracked metabolic fluxes, particularly glutamine and glycolytic pathways.
• Glutamate dehydrogenase was chemically inhibited to assess its role in EC fitness.

Main Results:

• WSS upregulated glutamine and glutamate metabolic pathways while downregulating glycolysis in ECs.
• Tracer metabolomics confirmed increased glutamine anaplerosis into the Krebs cycle and reduced glycolytic flux.
• Inhibition of glutamate dehydrogenase impaired EC fitness under WSS.

Conclusions:

• ECs under WSS preferentially utilize glutamine for central carbon metabolism, reducing reliance on glycolysis.
• Physical stimuli like WSS play a pivotal role in shaping EC metabolic responses and nutrient preferences.
• This study reveals key regulatory mechanisms governing EC metabolism in response to hemodynamic forces.