Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under...

Area of Science:

• Endocrinology
• Molecular Biology
• Vascular Biology

Background:

• Hyperglycemia contributes to microvascular complications, endothelial dysfunction, and inflammation.
• Cathepsin S (CTSS) activation in hyperglycemia is linked to inflammatory cytokine release.

Purpose of the Study:

• To investigate the immunomodulatory role of CTSS knockdown in high glucose-induced endothelial inflammation.
• To determine if blocking CTSS can alleviate hyperglycemia-related vascular complications and angiogenesis.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (HG) to mimic hyperglycemia.
• CTSS expression and inflammatory markers were measured; CTSS was downregulated using siRNA.
• NF-κB pathway activation, vascular endothelial markers, angiogenic activity, and complement activation (C3a, C5a) were assessed.

Main Results:

• HG treatment upregulated inflammatory cytokines and CTSS expression in HUVECs.
• siRNA-mediated CTSS knockdown significantly reduced inflammatory markers by inhibiting the NF-κB pathway.
• CTSS silencing decreased vascular endothelial markers, downregulated angiogenic activity, and reduced C3a/C5a activation.

Conclusions:

• CTSS silencing effectively mitigates hyperglycemia-induced vascular inflammation and associated complications.
• CTSS represents a promising therapeutic target for managing diabetes-induced microvascular damage.