Platelet P2Y(12) receptor influences the vessel wall response to arterial injury and thrombosis

Platelets are believed to play an important role in atherogenesis and the vessel response to vascular injury. The P2Y(12) receptor (P2Y(12)) plays a central role in amplifying platelet aggregation, dense granule and alpha-granule secretion, P-selectin expression, microparticle formation, and procoag...

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Published in:Circulation (New York, N.Y.) N.Y.), 2009-01, Vol.119 (1), p.116
Main Authors: Evans, D J W, Jackman, L E, Chamberlain, J, Crosdale, D J, Judge, H M, Jetha, K, Norman, K E, Francis, S E, Storey, R F
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis - pathology
Atherosclerosis - physiopathology
Blood Platelets - pathology
Blood Platelets - physiology
Bone Marrow Transplantation
Chlorides
Disease Models, Animal
Female
Femoral Artery - injuries
Femoral Artery - pathology
Femoral Artery - physiopathology
Ferric Compounds - toxicity
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Muscle, Smooth, Vascular - pathology
Muscle, Smooth, Vascular - physiopathology
Noxae - toxicity
P-Selectin - metabolism
Platelet Aggregation - physiology
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2Y12
Thrombosis - pathology
Thrombosis - physiopathology
Tunica Intima - injuries
Tunica Intima - pathology
Tunica Intima - physiopathology
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Summary:Platelets are believed to play an important role in atherogenesis and the vessel response to vascular injury. The P2Y(12) receptor (P2Y(12)) plays a central role in amplifying platelet aggregation, dense granule and alpha-granule secretion, P-selectin expression, microparticle formation, and procoagulant membrane changes, regardless of the activating stimulus. We hypothesized that P2Y(12) deficiency might reduce the vessel wall response to vascular injury as well as thrombosis in murine vascular injury models. P2Y(12)-deficient (-/-) mice and littermate controls (+/+) were bred on a C57 BL/6 background. In vivo murine models of arterial injury were employed alone and in combination with bone marrow transplantation to investigate the role of P2Y(12) in the vessel wall response to arterial injury and thrombosis. At 21 days after ferric chloride injury, neointima formation in P2Y(12)(-/-) arteries was significantly less than that observed in control strain arteries (P
ISSN:1524-4539
DOI:10.1161/CIRCULATIONAHA.107.762690