Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow
Abstract
Endothelial cells (ECs) 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. Here, we delineated the proteomic signatures of human umbilical vein endothelial cells (HUVECs) exposed to a protective flow (LSS) or a disturbed flow (OSS) in comparison to static conditions, using trapped ion mobility spectrometry coupled with parallel accumulation-serial fragmentation. OSS induced 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 Krüppel-like Factor 4 (KLF4) as an important transcriptional regulator of this effector cluster. Using a novel EC model, TeloHAECs, we demonstrated that KLF4 likely contributes to LSS-induced alignment and elongation by increasing the expression of CD34, HEG1, PI16, and ITGB4 and that KLF4 is involved in PI16 and ITGB4 expression. Collectively, these findings provide a robust discovery data set on EC proteomic profiles related to flow and a refined view of KLF4-associated regulatory signatures at the level of membrane protein-coding genes in response to LSS.
Related
- Ubiquitination regulation in coronary microcirculation dysfunction: focus on the endothelial cells.
- Vascular normalization confers an endothelial immune suppressive gene expression profile.
- Exosomal circ_0000387 Is Associated With Ovarian Cancer Metastatic Regulation Through IGF2BP3‐Related Signalling and Endothelial VWF Responses
- Expression of vascular endothelial growth factor A with rich vascularization in conjunctival papilloma.
- Regulation of calcium-sensing-receptor trafficking and cell-surface expression by GPCRs and RAMPs
BibTeX
@article{rethore2026proteomic,
title = {{Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow}},
author = {Léa Réthoré and Benjamin Barré and Anne-Laure Guihot and Linda Grimaud and Coralyne Proux and Alice Boissard and Cécile Henry and Catherine Guette and François Guillonneau and Daniel Henrion and Christian Legros and Claire Legendre},
journal = {Journal of Proteome Research},
year = {2026},
month = jul,
doi = {10.1021/acs.jproteome.5c01254},
url = {https://hal.science/hal-05757914v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow
AU - Léa Réthoré
AU - Benjamin Barré
AU - Anne-Laure Guihot
AU - Linda Grimaud
AU - Coralyne Proux
AU - Alice Boissard
AU - Cécile Henry
AU - Catherine Guette
AU - François Guillonneau
AU - Daniel Henrion
AU - Christian Legros
AU - Claire Legendre
PY - 2026
DA - 2026/07/06
JO - Journal of Proteome Research
DO - 10.1021/acs.jproteome.5c01254
UR - https://hal.science/hal-05757914v1
AB - Endothelial cells (ECs) 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. Here, we delineated the proteomic signatures of human umbilical vein endothelial cells (HUVECs) exposed to a protective flow (LSS) or a disturbed flow (OSS) in comparison to static conditions, using trapped ion mobility spectrometry coupled with parallel accumulation-serial fragmentation. OSS induced 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 Krüppel-like Factor 4 (KLF4) as an important transcriptional regulator of this effector cluster. Using a novel EC model, TeloHAECs, we demonstrated that KLF4 likely contributes to LSS-induced alignment and elongation by increasing the expression of CD34, HEG1, PI16, and ITGB4 and that KLF4 is involved in PI16 and ITGB4 expression. Collectively, these findings provide a robust discovery data set on EC proteomic profiles related to flow and a refined view of KLF4-associated regulatory signatures at the level of membrane protein-coding genes in response to LSS.
SN - 1535-3893
SN - 1535-3907
ER -