Under pressure: integrated endothelial cell response to hydrostatic and shear stresses

Area of Science:

• Cardiovascular Biology
• Mechanobiology
• Endothelial Cell Research

Background:

• Blood flow is crucial for endothelial cell (EC) function, but the combined effects of hemodynamic forces remain unclear.
• The role of hydrostatic pressure in EC responses to blood flow is understudied, despite its importance in vascular health and disease.

Purpose of the Study:

• To investigate how hydrostatic pressure influences endothelial cell responses to blood flow using in vitro models.
• To elucidate the interplay between pressure, shear stress, and EC transcriptional regulation.

Main Methods:

• Development of in vitro models to apply controlled pressure and flow conditions to endothelial cells.
• Analysis of EC alignment, density, and gene expression using bulk and single-cell RNA sequencing.
• Comparison of human EC responses with early mouse embryonic vascular development.

Main Results:

• Elevated hydrostatic pressure alters shear-induced EC alignment and increases EC density.
• Pressure modulates shear-induced EC signaling in a dose-dependent manner, complementing shear stress's primary role.
• Identified pressure-responsive transcriptional signatures in human ECs are conserved in early mouse vascular development.

Conclusions:

• Hydrostatic pressure acts synergistically with shear stress to regulate endothelial cell behavior and identity.
• An integrative approach to endothelial mechanotransduction, considering pressure alongside other forces, is essential.
• Pressure is associated with key transcriptional programs during embryonic vascular development, influencing arterial and hemogenic fates.