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Different Impacts of Cardiovascular Risk Factors on Oxidative Stress
Genotyping and Genetic Diagnosis Unit, Research Foundation of Hospital Clínico; Avenida Blasco Ibañez, 17, Valencia 46010, Spain
CIBER of obesity (CIBERob), Santiago de Compostela 15706, Spain
Hypertension Unit, Hospital Clinico; Avenida Blasco Ibañez, 17, Valencia 46010, Spain
Service of Endocrinology and Nutrition, Hospital Clínico Universitario, Avenida Blasco Ibañez, 17, Valencia 46010, Spain
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona 08017, Spain
Department of Biochemistry and Molecular Biology, University of Valencia, Avenida Blasco Ibañez, 17, Valencia 46010, Spain
* Author to whom correspondence should be addressed.
Received: 10 June 2011; in revised form: 1 September 2011 / Accepted: 7 September 2011 / Published: 20 September 2011
Abstract: 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.
Keywords: oxidative stress; glutathione peroxidase; superoxide dismutases; mRNA; hypertension; familial hypercholesterolemia; combined familial dyslipidemia
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Mansego, M.L.; Redon, J.; Martinez-Hervas, S.; Real, J.T.; Martinez, F.; Blesa, S.; Gonzalez-Albert, V.; Saez, G.T.; Carmena, R.; Chaves, F.J. Different Impacts of Cardiovascular Risk Factors on Oxidative Stress. Int. J. Mol. Sci. 2011, 12, 6146-6163.
Mansego ML, Redon J, Martinez-Hervas S, Real JT, Martinez F, Blesa S, Gonzalez-Albert V, Saez GT, Carmena R, Chaves FJ. Different Impacts of Cardiovascular Risk Factors on Oxidative Stress. International Journal of Molecular Sciences. 2011; 12(9):6146-6163.
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. 2011. "Different Impacts of Cardiovascular Risk Factors on Oxidative Stress." Int. J. Mol. Sci. 12, no. 9: 6146-6163.