Mast cell chymase and tryptase in abdominal aortic aneurysm formation

Abstract

Mast cells (MCs) are implicated in the pathogenesis of atherosclerosis and abdominal aortic aneurysm (AAA). MC-specific chymase and tryptase play important roles in inducing endothelial cell expression of adhesion molecules and chemokines to promote leukocyte recruitment, degrading matrix proteins and activating protease-activated receptors to trigger smooth muscle cell apoptosis, and activating other proteases to degrade medial elastin and to enhance angiogenesis. In experimental AAA, the absence or pharmacological inhibition of chymase or tryptase reduced AAA formation and associated arterial pathologies, proving that these MC proteases participate directly in AAA formation. Increased levels of these proteases in human AAA lesions and in plasma from AAA patients suggest that these proteases are also essential to human AAA pathogenesis. Development of chymase or tryptase inhibitors or their antibodies may have therapeutic potential among affected human subjects.

Figure 1

Role of mast cells, chymase, and tryptase in AAA. A representative AAA section from Apoe^−/− mouse is shown to the left to indicate toluidine blue staining of mast cells in the adventitia. Direct roles of chymase and tryptase are shown in the middle two frames and consequent roles of chymase and tryptase are shown in the right two frames.