Mansego Maria L, Redon Josep, Martinez-Hervas Sergio, Real Jose T, Martinez Fernando, Blesa Sebastian, Gonzalez-Albert Veronica, Saez Guillermo T, Carmena Rafael, Chaves Felipe J
Genotyping and Genetic Diagnosis Unit, Research Foundation of Hospital Clínico; Avenida Blasco Ibañez, 17, Valencia 46010, Spain; E-Mails:
Int J Mol Sci. 2011;12(9):6146-63. doi: 10.3390/ijms12096146. Epub 2011 Sep 20.
The objective of the study was to evaluate oxidative stress (OS) status in subjects with different cardiovascular risk factors. With this in mind, we have studied three models of high cardiovascular risk: hypertension (HT) with and without metabolic syndrome, familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) with and without insulin resistance. Oxidative stress markers (oxidized/reduced glutathione ratio, 8-oxo-deoxyguanosine and malondialdehide) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) and activation of both pro-oxidant enzyme (NAPDH oxidase components) and AGTR1 genes, as well as antioxidant enzyme genes (CuZn-SOD, CAT, GPX1, GSR, GSS and TXN) were measured in mononuclear cells of controls (n = 20) and patients (n = 90) by assessing mRNA levels. Activity of some of these antioxidant enzymes was also tested. An increase in OS and pro-oxidant gene mRNA values was observed in patients compared to controls. The hypertensive group showed not only the highest OS values, but also the highest pro-oxidant activation compared to those observed in the other groups. In addition, in HT a significantly reduced antioxidant activity and mRNA induction of antioxidant genes were found when compared to controls and the other groups. In FH and FCH, the activation of pro-oxidant enzymes was also higher and antioxidant ones lower than in the control group, although it did not reach the values obtained in hypertensives. The thioredoxin system was more activated in patients as compared to controls, and the highest levels were in hypertensives. The increased oxidative status in the presence of cardiovascular risk factors is a consequence of both the activation of pro-oxidant mechanisms and the reduction of the antioxidant ones. The altered response of the main cytoplasmic antioxidant systems largely contributes to OS despite the apparent attempt of the thioredoxin system to control it.
该研究的目的是评估具有不同心血管危险因素的受试者的氧化应激（OS）状态。考虑到这一点，我们研究了三种高心血管风险模型：伴有和不伴有代谢综合征的高血压（HT）、家族性高胆固醇血症（FH）以及伴有和不伴有胰岛素抵抗的家族性混合性高脂血症（FCH）。通过评估mRNA水平，在对照组（n = 20）和患者组（n = 90）的单核细胞中测量了氧化应激标志物（氧化型/还原型谷胱甘肽比率、8-氧代脱氧鸟苷和丙二醛）以及抗氧化酶三联体（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶）的活性，同时测量了促氧化酶（NAPDH氧化酶成分）和AGTR1基因以及抗氧化酶基因（CuZn-SOD、CAT、GPX1、GSR、GSS和TXN）的激活情况。还测试了其中一些抗氧化酶的活性。与对照组相比，患者中观察到OS和促氧化基因mRNA值增加。高血压组不仅显示出最高的OS值，而且与其他组相比促氧化激活程度也最高。此外，与对照组和其他组相比，在HT中发现抗氧化活性显著降低且抗氧化基因的mRNA诱导减少。在FH和FCH中，促氧化酶的激活也高于对照组，而抗氧化酶的激活低于对照组，尽管未达到高血压患者组的水平。与对照组相比，患者中的硫氧还蛋白系统激活程度更高，且高血压患者中水平最高。心血管危险因素存在时氧化状态的增加是促氧化机制激活和抗氧化机制降低的共同结果。尽管硫氧还蛋白系统明显试图控制它，但主要细胞质抗氧化系统的改变反应在很大程度上导致了OS。
