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

研究成果: Article査読

73 被引用数 (Scopus)

抄録

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, P<0.001). BrdU staining of arterial segments demonstrated a significantly lower incorporation in pCMV-PCS-transfected vessels (7.5±0.3% positive nuclei in vessel cells) than in pCMV-lacZ (50.7±9.6%, P<0.01). Moreover, 2 weeks after transfection, the PCS gene transfer resulted in a significant inhibition of neointimal formation (88% reduction in ratio of intima/media areas), whereas medial area was similar among the groups. Arterial segments transfected with pCMV-PCS produced significantly higher levels of 6-keto-PGF(1α), the main metabolite of PGI2, 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, P<0.001). In conclusion, this study demonstrated that an in vivo PCS gene transfer increased the production of PGI2 and markedly inhibited neointimal formation with accelerated reendothelialization in rat carotid arteries after balloon injury.

本文言語English
ページ(範囲)727-733
ページ数7
ジャーナルArteriosclerosis, thrombosis, and vascular biology
19
3
DOI
出版ステータスPublished - 03-1999
外部発表はい

All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

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