Key result
P2Y2R deficiency in mice led to a 3-fold decrease in mononuclear leukocyte intimal invasion and a >60% reduction in smooth muscle cell migration following vascular injury (p<0.05).
Why the study?
Does P2Y2R deficiency reduce neointimal hyperplasia following vascular injury in animal models?
Does P2Y2R deficiency reduce neointimal hyperplasia following vascular injury in animal models?
p-value: p=< 0.05
Loss- and gain-of-function models demonstrate that the P2Y2 receptor directly mediates neointimal hyperplasia after vascular injury, highlighting it as a potential target to prevent restenosis.
May position P2Y2R as a target to limit vascular remodeling; leaves open human translation.
Objectives: Extracellular nucleotide release at the site of arterial injury mediates the proliferation and migration of vascular smooth muscle cells. Our aim was to investigate the role of the P2Y₂ nucleotide receptor (P2Y₂R) in neointimal hyperplasia. Approach and Results: Vascular injury was induced by the implantation of a polyethylene cuff around the femoral artery in wild-type and P2Y₂R-deficient mice (P2Y₂R-/-). Electron microscopy was used to analyze monocyte and lymphocyte influx to the intima 36 h after injury. Compared to wild-type littermates, P2Y₂R-/- mice exhibited a 3-fold decreased number of mononuclear leukocytes invading the intima (p < 0.05). Concomitantly, the migration of smooth muscle cells was decreased by more than 60% (p < 0.05), resulting in a sharp inhibition of intimal thickening formation in P2Y₂R-/- mice (n = 15) 14 days after cuff placement. In vitro, loss of P2Y₂R significantly impaired monocyte migration in response to nucleotide agonists. Furthermore, transgenic rats overexpressing the P2Y₂R developed accelerated intimal lesions resulting in more than 95% luminal stenosis (p < 0.05, n = 10). Conclusions: Loss- and gain-of-function approaches established direct evidence for P2Y₂R involvement in neointimal hyperplasia. Specific anti-P2Y₂R therapies may be used against restenosis and bypass graft failure.
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Ağca et al. (2016) studied Neointimal hyperplasia following vascular injury. P2Y2R deficiency vs. Wild-type littermates was evaluated on Mononuclear leukocyte invasion and intimal thickening (p=< 0.05). P2Y2R deficiency in mice led to a 3-fold decrease in mononuclear leukocyte intimal invasion and a >60% reduction in smooth muscle cell migration following vascular injury (p<0.05).
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