Laminar shear stress promotes accumulation of polyunsaturated fatty acid in aortic endothelial cells through upregulation of LPCAT3 enzyme activity

Objective

Endothelial cells (ECs) play an important role in tissue homeostasis. Hemodynamic laminar shear stress are involved in both the physiological and pathological function of endothelial cells EC. Lipid metabolism has emerged as a potential regulator of EC function. Here, we aim to decipher the role of laminar shear stress in the regulation of lipid metabolism in human aortic endothelial cells.

Approach and results

Human aortic endothelial cells (HAOEC) were exposed to laminar shear stress, and lipid metabolism was analyzed. We found that laminar flow increased polyunsaturated fatty acid (PUFA) content in both neutral and polar lipids. These changes in fatty acid composition were dependent on lysophosphatidylcholine acyltransferase 3 (LPCAT3), which was specifically upregulated by laminar shear stress at both the mRNA and activity levels. Fatty acid uptake was also modulated by shear stress, partly via the LXR pathway. Notably, mechanical stimulation did not alter de novo fatty acid synthesis. However, fatty acid oxidation was upregulated in response to laminar shear stress, involving AMPK and ACC phosphorylation. These modifications in HAOEC fatty acid composition ultimately led to the release of a distinct pattern of lipid metabolites.

Conclusion

Overall these data revealed that laminar shear stress increased the turnover of FA acid and in human aortic endothelial cells through the activation of the LPCAT 3 enzyme.