Direct Evidence for P2Y2 Receptor Involvement in Vascular Response to Injury

Yuksel Agca, Shaomin Qian, Cansu Agca, Cheikh Seye

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)163-171
Number of pages9
JournalJournal of Vascular Research
DOIs
StateAccepted/In press - Oct 11 2016

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Purinergic P2Y2 Receptors
Blood Vessels
Nucleotides
Wounds and Injuries
Tunica Intima
Smooth Muscle Myocytes
Hyperplasia
Monocytes
Transgenic Rats
Mononuclear Leukocytes
Vascular System Injuries
Polyethylene
Femoral Artery
Vascular Smooth Muscle
Electron Microscopy
Pathologic Constriction

Keywords

  • Adenosine triphosphate
  • Arterial injury
  • Endothelial cells
  • Growth factor
  • Inflammation
  • Monocytes
  • P2Y receptors
  • Restenosis
  • Vascular biology

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Direct Evidence for P2Y2 Receptor Involvement in Vascular Response to Injury. / Agca, Yuksel; Qian, Shaomin; Agca, Cansu; Seye, Cheikh.

In: Journal of Vascular Research, 11.10.2016, p. 163-171.

Research output: Contribution to journalArticle

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abstract = "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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