Abstract 12457: Intracoronary Shear-related Upregulation of Platelet P-selectin, Platelet-monocyte Aggregation and Monocyte CD11b Despite the Use of Aspirin and Clopidogrel
Background: In vitro shear stress can cause platelet and leukocyte activation, both of which have been implicated in the development of atheromatous plaques. However, no studies have quantified the extent of shear-induced platelet and leukocyte activation within human coronary arteries, or the pathways affected by this process.
Methods: Blood was sampled from within coronary arteries proximal and distal to coronary lesions, and from the coronary sinus, in 20 patients with stable coronary disease taking both aspirin and clopidogrel. A novel method to estimate shear stress using computational fluid dynamics analysis of three-dimensional coronary angiographic images was developed. The effect of stenosis severity and calculated shear stress on in vivo platelet surface expression of P-selectin (CD62P), conformational activation of GPIIb-IIIa (PAC-1), platelet-monocyte aggregation (PM-Agg) and leukocyte CD11b expression were measured by flow cytometry, and soluble CD62P (sCD62P) by enzyme linked immunosorbent assay.
Results: Mean coronary artery % diameter stenosis was 53.1 ± 9.1 % and mean shear stress was 87.8 ± 128.8 Pa. Percentage diameter stenosis correlated with trans-lesion upregulation of platelet CD62P (r = 0.67, p < 0.01), PM-Agg (r = 0.60, p < 0.01) and monocyte CD11b (r = 0.70, p = 0.02). Similarly, calculated peak shear stress correlated with trans-lesion up-regulation of platelet CD62P (r = 0.55, p = 0.02), PM-Agg (r = 0.62, p < 0.01), and monocyte CD11b (r = 0.66, p = 0.04) but not PAC-1, sCD62P or granulocyte CD11b. Monocyte CD11b expression also correlated with PM-Agg (r = 0.72, p < 0.01).
Conclusions: Our results demonstrate for the first time shear-related platelet and monocyte activation within human coronary arteries in the presence of conventional anti-platelet therapy. Inhibition of platelet P-selectin, monocyte CD11b, and platelet-monocyte aggregation, but not GPIIb-IIIa, are implicated as potential therapeutic targets in this process.
- © 2010 by American Heart Association, Inc.