Data on TREM-1 activation destabilizing carotid plaques

Area of Science:

• Immunology and Inflammation
• Cardiovascular Biology
• Molecular Medicine

Background:

• Carotid stenosis is associated with plaque instability and inflammation.
• Tumor necrosis factor-alpha (TNF-α) plays a role in inflammatory processes.
• Triggering receptor expressed on myeloid cells-1 (TREM-1) is implicated in inflammatory responses.

Purpose of the Study:

• To investigate the role of TNF-α in regulating matrix metalloproteinases (MMPs) through TREM-1 in carotid stenosis.
• To examine the dose-response effects of TNF-α, TREM-1 antibody, and TREM-1/Fc fusion protein on MMP expression in vascular smooth muscle cells (VSMCs).
• To analyze the distribution and co-localization of M1 and M2 macrophages with TREM-1 in symptomatic carotid plaques.

Main Methods:

• Isolation of VSMCs from human carotid endarterectomy tissues.
• Treatment of VSMCs with TNF-α, TREM-1 antibody, and TREM-1/Fc fusion protein to assess MMP-1 and MMP-9 expression.
• Dual immunofluorescence staining to visualize CD86+ (M1) and CD206+ (M2) macrophages and TREM-1 co-localization in carotid plaques.

Main Results:

• TNF-α modulates the expression of MMP-1 and MMP-9 in VSMCs, a process influenced by TREM-1 signaling.
• Specific dose-dependent effects of TNF-α, TREM-1 antibody, and TREM-1/Fc on MMP expression were observed.
• Symptomatic carotid plaques exhibit distinct distributions of M1 and M2 macrophages, with TREM-1 co-localizing with these macrophage populations.

Conclusions:

• TNF-α signaling, mediated by TREM-1, contributes to the regulation of MMPs in the context of carotid stenosis.
• The findings suggest a complex interplay between TNF-α, TREM-1, macrophages, and MMPs in the pathogenesis of carotid plaque instability.
• Targeting the TNF-α/TREM-1 pathway may represent a potential therapeutic strategy for managing carotid stenosis.