TY - JOUR
T1 - Intracoronary shear-related up-regulation of platelet P-selectin and platelet-monocyte aggregation despite the use of aspirin and clopidogrel
AU - Yong, Andy S. C.
AU - Pennings, Gabrielle J.
AU - Chang, Michael
AU - Hamzah, Afiqah
AU - Chung, Tommy
AU - Qi, Miao
AU - Brieger, David
AU - Behnia, Masud
AU - Krilis, Steven A.
AU - Ng, Martin K. C.
AU - Lowe, Harry C.
AU - Kritharides, Leonard
PY - 2011/1/6
Y1 - 2011/1/6
N2 - Recent in vitro studies have shown that shear stress can cause platelet activation by agonist-independent pathways. However, no studies have assessed the extent of shear-induced platelet activationwithin human coronary arteries. We sampled blood from the coronary arteries proximal and distal to coronary lesions and from the coronary sinus in humans with stable coronary disease who were taking both aspirin and clopidogrel.Anovel, computationally based technique for estimating shear stress from 3-dimensional coronary angiographic images of these arteries was developed, and the effect of stenosis severity and calculated shear stress on in vivo platelet and related leukocyte activation pathways were determined.We provide evidence of intracoronary upregulation of platelet P-selectin, platelet-monocyte aggregation, and monocyte CD11b without platelet glycoprotein IIb-IIIa activation or soluble P-selectin up-regulation. This correlates with intracoronary stenosis severity and calculated shear stress and occurs despite the concurrent use of aspirin and clopidogrel. Our results show for the first time shear-related platelet and monocyte activation in human coronary arteries and suggest this as a potential therapeutic target that is resistant to conventional antiplatelet agents.
AB - Recent in vitro studies have shown that shear stress can cause platelet activation by agonist-independent pathways. However, no studies have assessed the extent of shear-induced platelet activationwithin human coronary arteries. We sampled blood from the coronary arteries proximal and distal to coronary lesions and from the coronary sinus in humans with stable coronary disease who were taking both aspirin and clopidogrel.Anovel, computationally based technique for estimating shear stress from 3-dimensional coronary angiographic images of these arteries was developed, and the effect of stenosis severity and calculated shear stress on in vivo platelet and related leukocyte activation pathways were determined.We provide evidence of intracoronary upregulation of platelet P-selectin, platelet-monocyte aggregation, and monocyte CD11b without platelet glycoprotein IIb-IIIa activation or soluble P-selectin up-regulation. This correlates with intracoronary stenosis severity and calculated shear stress and occurs despite the concurrent use of aspirin and clopidogrel. Our results show for the first time shear-related platelet and monocyte activation in human coronary arteries and suggest this as a potential therapeutic target that is resistant to conventional antiplatelet agents.
UR - http://www.scopus.com/inward/record.url?scp=78650991431&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-04-278812
DO - 10.1182/blood-2010-04-278812
M3 - Article
C2 - 20876457
AN - SCOPUS:78650991431
SN - 0006-4971
VL - 117
SP - 11
EP - 20
JO - Blood
JF - Blood
IS - 1
ER -