Shear Stress Conditioning Promotes a Pro-Inflammatory Response in Porcine Endocardial Endothelial Cells

Area of Science:

• Cardiovascular Biology
• Cellular Mechanotransduction

Background:

• Discrete subaortic stenosis (DSS) is a congenital heart defect affecting the left ventricular outflow tract (LVOT).
• Endocardial endothelial cells (EECs) are implicated in DSS, but their response to mechanical forces like shear stress is unclear.

Purpose of the Study:

• To investigate the hypothesis that EEC response to LVOT shear stress mediates DSS.
• To elucidate the cellular mechanisms underlying EECs' reaction to mechanical stress in the context of DSS.

Main Methods:

• Porcine EECs were subjected to controlled shear stress in cone-and-plate bioreactors.
• Proinflammatory cytokine concentrations were measured using Luminex assays.
• Bulk RNA sequencing analyzed genetic changes in shear-stressed EECs, including CD31 knockdown.

Main Results:

• Shear stress induced a proinflammatory response in EECs, with significant cytokine release.
• Activated signaling pathways included PI3K-AKT and TNF-a.
• CD31 was identified as a potential mediator of the proinflammatory response to shear stress.
• Immune cell differentiation pathways (Th1, Th2, Th17) were triggered.

Conclusions:

• Establishes a potential link between mechanical shear stress and the proinflammatory cascade in EECs.
• Suggests that EECs' response to shear stress is a key factor in the pathogenesis of DSS.