Functional interplay between platelet activation and endothelial dysfunction in patients with coronary heart disease.
Platelet-monocyte binding and surface P-selectin expression are sensitive markers of platelet activation. Endothelium-derived factors are known to inhibit platelet activation and may confer important anti-atherothrombotic effects. We assessed the relationship between platelet activation and endothelium-dependent vasomotion in patients with coronary heart disease (CHD). Twenty male patients with stable CHD were compared with 20 healthy men. Platelet-monocyte binding and platelet surface expression of P-selectin were assessed using two-colour flow cytometry on whole blood. Forearm blood flow was assessed in patients using venous occlusion plethysmography during intra-arterial infusions of substance P, acetylcholine and sodium nitroprusside. Platelet activation was higher in patients than healthy men (platelet-monocyte binding, 27 +/- 3 vs. 20 +/- 1%; P < 0.05). In patients with CHD, there was an inverse correlation between maximal substance P induced vasodilatation and both platelet-monocyte binding (P = 0.003) and P-selectin expression (P = 0.02). A similar correlation was observed between platelet-monocyte binding and the vasomotor response to acetylcholine (P = 0.08) but not with sodium nitroprusside. In patients with stable coronary heart disease, there is a strong inverse relationship between markers of platelet activation and endothelium-dependent vasomotor function. This may explain the pathophysiological mechanism linking endothelial vasomotor dysfunction and the risk of acute atherothrombotic events.
Robinson
S D
SD
Centre for Cardiovascular Science, University of Edinburgh, UK. simon.robinson@ed.ac.uk
Harding
S A
SA
Cummins
P
P
Din
J N
JN
Sarma
J
J
Davidson
I
I
Fox
K A A
KA
Boon
N A
NA
Newby
D E
DE
D000704:Analysis of Variance; D050197:Atherosclerosis / Q000503:physiopathology*; D002450:Cell Communication / Q000502:physiology*; D003327:Coronary Disease / Q000097:blood / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005434:Flow Cytometry; D018056:Hemorheology / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology*; D010973:Platelet Adhesiveness / Q000502:physiology; D010991:Plethysmography; D012044:Regression Analysis; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D019007:P-Selectin; D014665:Vasodilator Agents