Proteomic profiling of Endothelial Cells Under Laminar Shear Stress Reveals KLF4-mediated Membrane Protein Regulation Compared to Oscillatory Flow

ABSTRACT: Endothelial cells (EC) are key regulators in vascular homeostasis, and their physiological state depends on hemodynamic forces produced by the blood flow. Laminar shear stress (LSS) maintains endothelial integrity, whereas oscillatory shear stress (OSS) leads to endothelial dysfunction and subsequently to cardiovascular disease. To clarify how these flow patterns regulate EC responses, we conducted deep proteomic profiling of Human umbilical vascular endothelial cells cultivated under LSS or OSS versus static conditions, using trapped ion mobility spectrometry coupled with parallel accumulation-serial fragmentation. OSS induced only limited changes in cell morphology and the proteomic profile, whereas LSS triggered major modifications in cell shape and a proteomic signature related to the cell surface and extracellular matrix. Membrane subproteomic profiling confirmed the identification of membrane effectors involved in flow-mediated responses and in silico integrating promoter analysis suggested KLF4 as the main transcriptional regulator of this effector cluster. Using the TeloHAEC model, we demonstrated that KLF4 drives LSS-induced alignment and elongation by increasing the expression of CD34, HEG1, PI16 and ITGB4. Collectively, these findings provide a comprehensive resource on EC proteomic profiles related to flow and reinforce the central role of KLF4, as a key player in membrane remodeling in response to LSS.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Endothelial Cell, Umbilical Vein Endothelial Cell Line

DISEASE(S): Atherosclerosis

SUBMITTER: Benjamin Barre  

LAB HEAD: Christian Legros

PROVIDER: PXD072355 | Pride | 2026-09-11

REPOSITORIES: Pride