Rictor maintains endothelial integrity under shear stress.

Area of Science:

• Cardiovascular Biology
• Cellular Biology
• Molecular Medicine

Background:

• Low shear stress (LSS) initiates cardiovascular diseases like atherosclerosis and hypertension.
• LSS activates the mTORC2 pathway, involving Rictor, essential for vascular development.
• The role of Rictor in endothelial homeostasis and response to LSS is not fully understood.

Purpose of the Study:

• Investigate Rictor's role in maintaining endothelial integrity.
• Determine Rictor's involvement in LSS-induced endothelial injury.
• Clarify Rictor's mechanism in regulating endothelial markers under LSS.

Main Methods:

• Generated a mouse model with endothelial Rictor knockout.
• Utilized scanning and transmission electron microscopy to assess endothelial integrity.
• Conducted in vitro studies using human umbilical vein endothelial cells with Rictor knockdown via siRNA.

Main Results:

• Rictor deficiency disrupted endothelial monolayer integrity and expanded cell junctions in mice.
• LSS induced vascular endothelial-cadherin (VE-cadherin) translocation and actin disruption in vitro.
• Rictor knockdown exacerbated VE-cadherin translocation and inhibited von Willebrand factor (VWF) upregulation under LSS.

Conclusions:

• Endothelial Rictor is vital for maintaining vascular integrity under physiological conditions.
• Rictor mediates LSS-induced endothelial injury by regulating adherens junctions and VWF.
• Targeting Rictor may offer therapeutic strategies for LSS-related vascular diseases.