Different impacts of cardiovascular risk factors on oxidative stress.
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.
Genotyping and Genetic Diagnosis Unit, Research Foundation of Hospital Clínico; Avenida Blasco Ibañez, 17, Valencia 46010, Spain; E-Mails:  Sebastian.Blesa@uv.es  (S.B);  veronica.gonzalez@uv.es  (V.G.-A.);  felipe.chaves@uv.es  (F.J.C.).
Maria L
ML
Mansego
Josep
J
Redon
Sergio
S
Martinez-Hervas
Jose T
JT
Real
Fernando
F
Martinez
Sebastian
S
Blesa
Veronica
V
Gonzalez-Albert
Guillermo T
GT
Saez
Rafael
R
Carmena
Felipe J
FJ
Chaves
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D005981:Glutathione Synthase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics / Q000378:metabolism; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C086986:CYBA protein, human; D005980:Glutathione Reductase; D005981:Glutathione Synthase; D003849:Deoxyguanosine; D005978:Glutathione