Low shear stress damages endothelial function through STAT1 in endothelial cells (ECs)

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Function
• Molecular Mechanisms of Atherosclerosis

Background:

• Low shear stress (LSS) is associated with atherosclerotic lesion development.
• Signal transducer and activator of transcription 1 (STAT1) is implicated in cardiovascular disease, but its role in LSS is unclear.

Purpose of the Study:

• To investigate the relationship between LSS and STAT1 activation in endothelial cells (ECs).
• To elucidate the mechanism by which LSS affects endothelial function via STAT1.

Main Methods:

• Endothelial cells were subjected to LSS in vitro.
• Protein expression and phosphorylation analyzed via Western blotting.
• Immunofluorescence used on human coronary arteries.
• Endothelial function assessed using dihydroethidium assay, real-time PCR, and NO-sensitive fluorophore.

Main Results:

• LSS induced STAT1 (Tyr701) phosphorylation in ECs and increased intimal STAT1 expression in human coronary arteries.
• STAT1 phosphorylation was positively regulated by inhibitor of nuclear factor kappa-B kinase ε (IKKε).
• Silencing STAT1 (siSTAT1) reversed LSS-induced inflammatory factor expression, increased reactive oxygen species (ROS), and decreased nitric oxide (NO) release, while upregulating heme oxygenase-1 (HO-1) and downregulating eNOS Thr495 phosphorylation.

Conclusions:

• LSS-mediated endothelial cell injury is linked to STAT1 activation.
• Targeting STAT1 expression or activation may be a potential therapeutic approach for atherosclerosis.