Global improvement of vascular function and redox state with low-dose folic acid - Implications for folate therapy in patients with coronary artery disease
Global improvement of vascular function and redox state with low-dose folic acid - Implications for folate therapy in patients with coronary artery disease
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DOI：
10.1161/circulationaha.106.679084
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发表时间：
2007-05-01
期刊：
影响因子：
37.8
通讯作者：
Channon, Keith M.
中科院分区：
文献类型：
--
作者：
Shirodaria, Cheerag;Antoniades, Charalambos;Channon, Keith M.
背景-尽管膳食叶酸强化可降低血浆同型半胱氨酸水平，并可能降低心血管风险，但大剂量叶酸治疗似乎并不改变临床结果。叶酸及其主要循环代谢产物5-甲基四氢叶酸可改善血管功能，但叶酸剂量与血管功能相关的机制尚不清楚。我们比较了叶酸对人体血管的影响，使用药理学高剂量与低剂量的治疗，相当于膳食叶酸forwarding.Methods和结果-五十六非叶酸强化冠心病患者随机接受低剂量（400微克/天）或高剂量（5毫克/天）叶酸或安慰剂7周前冠状动脉旁路移植术。在治疗前后通过磁共振成像对血管功能进行量化。在隐静脉和乳内动脉段测定血管超氧化物歧化酶和一氧化氮的生物利用度。低剂量叶酸增加了一氧化氮介导的内皮依赖性血管反应，减少了血管超氧化物的产生，并通过辅助因子四氢生物蝶呤的可用性改善了内皮一氧化氮合酶的酶偶联。与低剂量治疗相比，高剂量治疗的这些参数没有进一步改善。而血浆5-methyltetrahydrofolate增加proportionarity与治疗剂量的叶酸，血管组织5-methyltetrahydrofolate显示没有进一步的增量与高剂量相比，低剂量的叶酸acid.Conclusions -低剂量的叶酸治疗，相当于每日摄入量和膳食强化，通过对内皮型一氧化氮合酶和血管氧化应激的影响，改善血管功能。高剂量叶酸治疗没有额外的好处。这些直接的血管效应与5-甲基四氢叶酸的血管组织水平而不是血浆水平有关。高剂量叶酸治疗可能不会给已经接受叶酸补充的受试者带来进一步的益处。
Background - Although dietary folate fortification lowers plasma homocysteine and may reduce cardiovascular risk, high-dose folic acid therapy appears to not alter clinical outcome. Folic acid and its principal circulating metabolite, 5-methyltetrahydrofolate, improve vascular function, but mechanisms relating folate dose to vascular function remain unclear. We compared the effects of folic acid on human vessels using pharmacological high-dose versus low-dose treatment, equivalent to dietary folate fortification.Methods and Results - Fifty-six non-folate-fortified patients with coronary artery disease were randomized to receive low-dose (400 mu g/d) or high-dose (5 mg/d) folic acid or placebo for 7 weeks before coronary artery bypass grafting. Vascular function was quantified by magnetic resonance imaging before and after treatment. Vascular superoxide and nitric oxide bioavailability were determined in segments of saphenous vein and internal mammary artery. Low-dose folic acid increased nitric oxide - mediated endothelium-dependent vasomotor responses, reduced vascular superoxide production, and improved enzymatic coupling of endothelial nitric oxide synthase through availability of the cofactor tetrahydrobiopterin. No further improvement in these parameters occurred with high-dose compared with low-dose treatment. Whereas plasma 5-methyltetrahydrofolate increased proportionately with treatment dose of folic acid, vascular tissue 5-methyltetrahydrofolate showed no further increment with high-dose compared with low-dose folic acid.Conclusions - Low-dose folic acid treatment, comparable to daily intake and dietary fortification, improves vascular function through effects on endothelial nitric oxide synthase and vascular oxidative stress. High-dose folic acid treatment provides no additional benefit. These direct vascular effects are related to vascular tissue levels of 5-methyltetrahydrofolate rather than plasma levels. High-dose folic acid treatment likely confers no further benefit in subjects already receiving folate supplementation.