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• W1986244797 abstract "1 Tetrahydrobiopterin (BH4) is an essential cofactor that maintains the normal function of endothelial nitric oxide (NO) synthase. Restenosis is a key complication after transluminal angioplasty. Guanosine 5′-triphosphate-cyclohydrolase I (GTPCH) is the first rate-limiting enzyme for de novo BH4 synthesis. However, the role of GTPCH in restenosis is not fully understood. The present study tested the hypothesis that endothelial-targeted GTPCH overexpression retards neointimal formation, a hallmark of restenosis, in mouse carotid artery. 2 Transluminal wire injury was induced in the left carotid arteries of adult male wild-type C57BL/6 (WT) and endothelial GTPCH transgenic (Tg-GCH) mice. Re-endothelialization was confirmed with in vivo Evans blue staining. Endothelium-dependent and -independent relaxations were measured using isometric tension recording. Morphological analysis was performed 2 and 4 weeks after carotid injury to assess neointimal formation. Fluorescence-based high-performance liquid chromatography (HPLC) was used to determine GTPCH activity and BH4 levels. Basal NO release following carotid injury was assessed by NG-nitro-l-arginine methyl ester-induced vascular contraction. 3 The endothelium was completely removed upon transluminal wire injury and full re-endothelialization was achieved at Day 10. Endothelium-dependent relaxation was impaired 10 days and 4 weeks after carotid injury, whereas endothelium-independent relaxation remained unaffected. Morphological analysis revealed that the endothelial-specific overexpression of GTPCH reduced neointimal formation and medial hypertrophy 2 and 4 weeks after carotid injury. Both arterial GTPCH enzyme activity and BH4 levels were significantly elevated in Tg-GCH mice compared with WT mice and basal NO release of the injured carotid artery tended to increase in Tg-GCH mice. 4 These findings suggest that the endothelial overexpression of GTPCH increased endothelial BH4 synthesis and played a preventive role in neointimal formation induced by endothelium denudation." @default.
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• W1986244797 date "2007-12-01" @default.
• W1986244797 modified "2023-10-18" @default.
• W1986244797 title "ENDOTHELIUM-TARGETED TRANSGENIC GTP-CYCLOHYDROLASE I OVEREXPRESSION INHIBITS NEOINTIMA FORMATION IN MOUSE CAROTID ARTERY" @default.
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• W1986244797 doi "https://doi.org/10.1111/j.1440-1681.2007.04719.x" @default.
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