Mast cell tryptase deficiency attenuates mouse abdominal aortic aneurysm formation

Area of Science:

• Vascular Biology
• Immunology
• Protease Function

Background:

• Mast cells (MCs) are implicated in abdominal aortic aneurysm (AAA) development through mediator production.
• Tryptase, a key MC granule protein, influences processes vital to AAA pathogenesis, including leukocyte recruitment and angiogenesis.

Purpose of the Study:

• To investigate the direct role of tryptase in the formation and progression of abdominal aortic aneurysms.

Main Methods:

• Immunohistochemistry on human and mouse AAA lesions.
• Analysis of serum tryptase levels and AAA expansion rates in patients.
• Utilizing mast cell protease-6-deficient (Mcpt6(-/-)) mice in experimental AAA models.
• Investigating the impact of tryptase deficiency on cellular and molecular pathways in AAA pathogenesis.

Main Results:

• Enhanced tryptase staining observed in human and mouse AAA lesions.
• Serum tryptase levels significantly correlated with AAA expansion rate and clinical outcomes.
• Mcpt6(-/-) mice were protected from AAA development, exhibiting reduced inflammation and apoptosis.
• Tryptase deficiency impacted endothelial cell function, monocyte transmigration, and smooth muscle cell apoptosis.

Conclusions:

• Mast cell tryptase plays a direct role in the pathogenesis of experimental AAAs.
• Serum tryptase levels may serve as a novel biomarker for monitoring abdominal aortic aneurysm expansion.