Recruitment of circulating inflammatory cells to human coronary artery endothelium: A potential role for mast cell tryptase.

摘要

Inflammation has recently been identified as a risk factor and potential propagative factor for a variety of cardiovascular diseases including atherosclerosis. The presence of increased mast cell numbers in atherosclerotic plaques suggests that they play a role in mediating inflammation in this disease process. Platelet aggregation and mural thrombosis are universal features in the initiation and generation of atherosclerotic lesions. The rupture of the atherosclerotic plaque results in a coronary ischemic event in which human coronary artery endothelial cells (HCAEC) in the ischemic area would be exposed to increased thrombin concentrations and tryptase released by activated mast cells present in the plaque.; Studies detailed here discuss the inflammatory changes seen in HCAEC following thrombin or tryptase stimulation. Treatment of HCAEC with either of these proteases activates calcium-independent phospholipase A2 (iPLA2), resulting in an accumulation of membrane phospholipid-derived metabolites, such as platelet-activating factor (PAF) and arachidonic acid. Studies identified that a novel protein kinase C (PKC) is responsible for modulation of iPLA2 activation, possibly via phosphorylation. Protease stimulation also increases cell-surface P-selectin expression and neutrophil adherence, events that play a role in propagating the inflammatory response.; Additionally, a mast cell precursor population of CD133 positive cells was isolated from human umbilical cord blood. Results suggest that these cells adhere to, and migrate across, HCAEC in a process which is dependent, at least in part, on the interaction of PAF, expressed by tryptase stimulated HCAEC, and the PAF receptor (PTAFR), present on CD133 positive cells.; These studies present roles for the proteases thrombin and tryptase in the initiation and propagation of atherosclerotic plaque inflammation and for PAF in the adherence and migration of mast cell precursors.