Short-term hyperglycemia increases arterial superoxide production and iron dysregulation in atherosclerotic monkeys.
Short-term hyperglycemia increases arterial superoxide production and iron dysregulation in atherosclerotic monkeys.
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DOI：
10.1016/j.metabol.2010.11.003
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发表时间：
2011-08
影响因子：
9.8
通讯作者：
Wagner, Janice D.
中科院分区：
文献类型：
--
作者：
Rowe, Patrick A.;Kavanagh, Kylie;Zhang, Li;Harwood, H. James, Jr.;Wagner, Janice D.
糖尿病患者动脉粥样硬化性血管疾病的发病率和严重程度增加，部分原因是活性氧（ROS）产生增加。此前，我们发现，在喂食致动脉粥样硬化饮食的猴子中，链脲佐菌素诱发糖尿病六个月后，动脉粥样硬化和动脉蛋白氧化均增加，其模式表明氧化还原活性过渡金属的参与。本研究的目的是确定短期（一个月）高血糖是否会在动脉粥样硬化出现差异之前增加氧化应激并调节铁代谢失调。根据饮食史和血浆脂质对预先存在动脉粥样硬化的食蟹猴进行分层，并接受链脲佐菌素（STZ-DM；n=10）或载体（对照；n=10）。糖尿病诱导一个月后，收集血液和动脉样本。对照组和 STZ-DM 之间的血浆脂蛋白胆固醇、动脉胆固醇和动脉粥样硬化没有差异。然而，与对照组相比，STZ-DM 患者的血浆脂质过氧化物升高了 137%（p<0.01），动脉超氧化物升高了 47%（p<0.05），血浆铁蛋白（全身铁储存指标）升高了 46%（p<0.05），主动脉粥样硬化病变内的铁沉积更为普遍。 STZ-DM 患者的动脉抗氧化酶、超氧化物歧化酶、过氧化氢酶和血红素加氧酶 1 水平并不较高，尽管超氧化物水平较高，这表明抗氧化反应受损。 ROS 的增加先于动脉粥样硬化的差异，支持 ROS 作为糖尿病血管疾病的起始事件。需要进一步的研究来确定铁储存和动脉铁沉积的增加是否会促进超氧化物形成羟自由基并加速糖尿病血管损伤。
The incidence and severity of atherosclerotic vascular disease is increased in diabetics, in part due to increased production of reactive oxygen species (ROS). Previously we found both increased atherosclerosis and arterial protein oxidation six months after streptozotocin-induced diabetes in monkeys fed an atherogenic diet, the pattern of which was indicative of redox-active transition metal involvement. The goal of this study was to determine if short-term (one month) hyperglycemia increases oxidative stress and dysregulates iron metabolism prior to differences in atherosclerosis. Cynomolgus monkeys with pre-existing atherosclerosis were stratified by dietary history and plasma lipids and received either streptozotocin (STZ-DM; n=10) or vehicle (control; n=10). One month after diabetes induction, blood and artery samples were collected. There were no differences in plasma lipoprotein cholesterol, arterial cholesterol, and atherosclerosis between control and STZ-DM. However, plasma lipid peroxides were elevated 137% (p<0.01), arterial superoxide was increased 47% (p<0.05), plasma ferritin, an indicator of whole-body iron stores, was 46% higher (p<0.05), and iron deposition within aortic atherosclerotic lesions was more prevalent in STZ-DM compared to controls. Arterial levels of the antioxidant enzymes, superoxide dismutase, catalase, and heme oxygenase-1 were not higher in STZ-DM, even though superoxide was higher, suggesting impaired antioxidant response. The increase in ROS prior to differences in atherosclerosis supports ROS as an initiating event in diabetic vascular disease. Further studies are needed to determine if increases in iron stores and arterial iron deposition promotes hydroxyl radical formation from superoxide and accelerates diabetic vascular damage.
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