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(Circulation. 2009;119:116-122.)
© 2009 American Heart Association, Inc.

Vascular Medicine

Platelet P2Y₁₂ Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis

D.J.W. Evans, PhD; L.E. Jackman, BSc; J. Chamberlain, PhD; D.J. Crosdale, PhD; H.M. Judge, PhD; K. Jetha, PhD; K.E. Norman, PhD; S.E. Francis, PhD; R.F. Storey, MD

From the Cardiovascular Research Unit, University of Sheffield, Sheffield, UK.

Correspondence to Dr Robert F. Storey, Cardiovascular Research Unit, School of Medicine and Biomedical Sciences, Beech Hill Rd, Sheffield, S10 2RX, UK. E-mail r.f.storey{at}sheffield.ac.uk

Received January 9, 2008; accepted October 14, 2008.

Background— Platelets are believed to play an important role in atherogenesis and the vessel response to vascular injury. The P2Y₁₂ receptor (P2Y₁₂) plays a central role in amplifying platelet aggregation, dense granule and -granule secretion, P-selectin expression, microparticle formation, and procoagulant membrane changes, regardless of the activating stimulus. We hypothesized that P2Y₁₂ deficiency might reduce the vessel wall response to vascular injury as well as thrombosis in murine vascular injury models.

Methods and Results— P2Y₁₂-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 P2Y₁₂ in the vessel wall response to arterial injury and thrombosis. At 21 days after ferric chloride injury, neointima formation in P2Y₁₂^–/– arteries was significantly less than that observed in control strain arteries (P<0.025). In agreement with this, the intima-media ratio was significantly greater in femoral wire-injured arteries from P2Y₁₂^+/+ compared with P2Y₁₂^–/– animals (P<0.05). Bone marrow transplantation was used to examine the importance of vessel wall P2Y₁₂ versus platelet P2Y₁₂. Analysis of arterial sections from chimeric animals at 21 days after injury revealed a smaller intima-media ratio in –/– to +/+ animals than in the positive (+/+ to +/+) control group (P<0.01).

Conclusions— These data demonstrate a role for platelet P2Y₁₂ in the vessel wall response to arterial injury and thrombosis. This illustrates the manner in which platelets may contribute to atherogenesis and restenosis.

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Circulation 2009 119: 1-4. [Extract] [Full Text]