Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression

Area of Science:

• Biomedical research
• Cardiovascular science
• Immunology

Background:

• Soluble P-selectin (sP-selectin) is a biomarker for inflammatory diseases and promotes atherosclerosis by increasing leukocyte recruitment.
• Understanding sP-selectin's role in atherosclerotic plaque progression is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the impact of chronically elevated soluble P-selectin levels on the progression of atherosclerotic plaque disease.
• To determine if sP-selectin influences plaque phenotype and stability in a murine model.

Main Methods:

• Apoe-/- mice on a high-fat diet (HFD) received daily injections of recombinant dimeric murine P-selectin for 8 or 16 weeks.
• A plaque remodelling model using sm22α-hDTR Apoe-/- mice on HFD with diphtheria toxin was employed to assess atherothrombosis.
• Plasma and plaque analyses were conducted to evaluate inflammatory markers, cell content, and plaque composition.

Main Results:

• sP-selectin treatment did not alter plaque mass or aortic lipid content in either mouse model.
• Increased plasma MCP-1 and plaque CD45 content were observed in Apoe-/- HFD mice treated with sP-selectin.
• In the plaque remodelling model, sP-selectin induced a shift towards an unstable plaque phenotype, characterized by increased macrophage accumulation and reduced collagen content, lowering the plaque stability index.

Conclusions:

• Chronically elevated soluble P-selectin levels promote the progression of an unstable atherosclerotic plaque phenotype.
• sP-selectin contributes to atherothrombosis by modulating plaque composition and stability.
• These findings highlight sP-selectin as a potential therapeutic target in managing atherosclerotic cardiovascular diseases.