Department of Pathology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
Metabolism. 2011 Aug;60(8):1070-80. doi: 10.1016/j.metabol.2010.11.003. Epub 2011 Jan 19.
The incidence and severity of atherosclerotic vascular disease are increased in diabetic patients, in part because of increased production of reactive oxygen species (ROS). Previously, we found both increased atherosclerosis and arterial protein oxidation 6 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 (1 month) hyperglycemia increases oxidative stress and dysregulates iron metabolism before differences in atherosclerosis. Cynomolgus monkeys with preexisting 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 < .01); arterial superoxide was increased 47% (P < .05); plasma ferritin, an indicator of whole-body iron stores, was 46% higher (P < .05); and iron deposition within aortic atherosclerotic lesions was more prevalent in STZ-DM compared with controls. Arterial levels of the antioxidant enzymes, superoxide dismutase, catalase, and heme oxygenase-1 were not higher in STZ-DM, although superoxide was higher, suggesting impaired antioxidant response. The increase in ROS before 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 promote hydroxyl radical formation from superoxide and accelerate diabetic vascular damage.
在糖尿病患者中，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）的产生增加。先前，我们发现，在喂食动脉粥样硬化饮食的猴子中，糖尿病诱导 6 个月后，动脉粥样硬化和动脉蛋白氧化均增加，其模式表明涉及氧化还原活性过渡金属。本研究的目的是确定短期（1 个月）高血糖是否会在动脉粥样硬化发生差异之前增加氧化应激和扰乱铁代谢。根据饮食史和血浆脂质，将患有预先存在动脉粥样硬化的食蟹猴分层，并分别接受链脲佐菌素（STZ-DM；n = 10）或载体（对照；n = 10）治疗。糖尿病诱导 1 个月后，收集血液和动脉样本。对照组和 STZ-DM 组之间的血浆脂蛋白胆固醇、动脉胆固醇和动脉粥样硬化无差异。然而，血浆脂质过氧化物增加了 137%（P <.01）；动脉超氧化物增加了 47%（P <.05）；血浆铁蛋白（一种全身铁储存的指标）升高了 46%（P <.05）；并且 STZ-DM 组主动脉粥样硬化病变内的铁沉积比对照组更为普遍。尽管超氧化物增加，但 STZ-DM 中抗氧化酶超氧化物歧化酶、过氧化氢酶和血红素加氧酶-1 的动脉水平没有升高，这表明抗氧化反应受损。在动脉粥样硬化差异之前，ROS 的增加支持 ROS 作为糖尿病血管疾病的起始事件。需要进一步研究以确定铁储存和动脉铁沉积的增加是否会促进超氧化物产生羟基自由基并加速糖尿病血管损伤。
