Antiangiogenic Effect of Platelet P2Y12 Inhibitor in Ischemia-Induced Angiogenesis in Mice Hindlimb

Biomed Res Int. 2021 Apr 8:2021:5529431. doi: 10.1155/2021/5529431. eCollection 2021.

Abstract

Purpose: Postischemic inflammation induces angiogenesis, while platelet P2Y12 inhibitors can alleviate this inflammation. Therefore, we studied the potential effects of P2Y12 inhibitor, ticagrelor, on angiogenesis in a mouse model of hindlimb ischemia.

Methods: Laser Doppler perfusion imaging and capillary density measurement were used for angiogenesis quantified. Immunofluorescence was used to detect the level of CD31. The mice muscle was harvested for enzyme-linked immunosorbent (ELISA) assay of interleukin- (IL) 10 activity and Western blot determination of vascular endothelial growth factor (VEGF) production.

Results: Ischemic hindlimb angiogenesis was sharply decreased in IL-10+/+ mice than IL-10-/- mice. Ticagrelor inhibited angiogenesis and blood reperfusion recovery significantly elevated the levels of IL-10 and decreased the expression of VEGF in the IL-10+/+ mouse ischemic hindlimb, which were abolished in IL-10-deficient (IL-10-/-) C57BL/6J mice.

Conclusion: The study underscores that the effect of ticagrelor antiangiogenic function is related with the higher IL-10 expression.

Publication types

  • Retracted Publication

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Capillaries / pathology
  • Hindlimb / blood supply*
  • Interleukin-10 / metabolism
  • Ischemia / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscles / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Perfusion
  • Platelet Aggregation Inhibitors / pharmacology*
  • Purinergic P2Y Receptor Antagonists / pharmacology*
  • Receptors, Purinergic P2Y12 / metabolism*
  • Ticagrelor / pharmacology
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Vascular Endothelial Growth Factors
  • Interleukin-10
  • Ticagrelor