Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury

Yasushi Numaguchi, Keiji Naruse, Mitsunori Harada, Hiroyuki Osanai, Shinji Mokuno, Kichiro Murase, Hideo Matsui, Yukio Toki, Takayuki Ito, Kenji Okumura, Tetsuo Hayakawa

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Abstract

Prostacyclin (PGI2), a metabolite of arachidonic acid, has the vasoprotective effects of vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation. We hypothesized that an overexpression of endogenous PGI2 may accelerate the recovery from endothelial damage and inhibit neointimal formation in the injured artery. To test this hypothesis, we investigated in vivo transfer of the PGI2 synthase (PCS) gene into balloon-injured rat carotid arteries by a nonviral lipotransfection method. Seven days after transfection, a significant regeneration of endothelium was observed in the arteries transfected with a plasmid carrying the rat PCS gene (pCMV-PCS), but little regeneration was seen in those with the control plasmid carrying the lacZ gene (pCMV-lacZ) (percent luminal circumference lined by newly regenerated endothelium: 87.1±6.9% in pCMV-PCS-transfected vessels and 6.9±0.2% in pCMV-lacZ vessels, P2, compared with the segments transfected with pCMV-lacZ (10.2±0.55 and 2.1±0.32 ng/mg tissue for pCMV-PCS and pCMV-placZ, P2 and markedly inhibited neointimal formation with accelerated reendothelialization in rat carotid arteries after balloon injury.

Original languageEnglish
Pages (from-to)727-733
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume19
Issue number3
Publication statusPublished - Mar 1999
Externally publishedYes

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Keywords

  • Balloon injury
  • Gene therapy
  • Prostacyclin
  • Prostacyclin synthase
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Numaguchi, Y., Naruse, K., Harada, M., Osanai, H., Mokuno, S., Murase, K., Matsui, H., Toki, Y., Ito, T., Okumura, K., & Hayakawa, T. (1999). Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal formation in rat carotid arteries after balloon injury. Arteriosclerosis, Thrombosis, and Vascular Biology, 19(3), 727-733.