Increased formation of distinct F-2 isoprostanes in hypercholesterolemia

Article; Proceedings Paper

关键词: LOW-DENSITY-LIPOPROTEIN;    ACUTE MYOCARDIAL-INFARCTION;    VITAMIN-E CONSUMPTION;    STRESS IN-VIVO;    OXIDANT STRESS;    CORONARY-DISEASE;    8-EPI-PROSTAGLANDIN F2-ALPHA;    PROSTANOIDS F2-ISOPROSTANES;    CARDIOVASCULAR-DISEASE;    PLATELET ACTIVATION;   

DOI  :  10.1161/01.CIR.98.25.2822

来源: SCIE

【 摘 要 】

Background-F-2 isoprostanes are stable, free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. Methods and Results-Specific assays were developed by use of mass spectrometry for the F-2 isoprostanes iPF(2 alpha)-III and iPF(2 alpha)-VI and arachidonic acid (AA). Urinary excretion of the 2 F-2 isoprostanes was significantly increased in hypercholesterolemic patients, whereas substrate AA in urine did not differ between the groups. iPF(2a)-III (pmol/mmol creatinine) was elevated (P<0.0005) in homozygous familial hypercholesterolemic (HFH) patients (85+/-5.5; n=38) compared with age- and sex-matched normocholesterolemic control subjects (58+/-4.2; n=38), as were levels of iPF(2 alpha)-VI (281+/-22 versus 175+/-13; P<0.0005). Serum cholesterol correlated with urinary iPF(2 alpha)-III (r=0.41; P<0.02) and iPF(2 alpha)-VI (r=0.39; P<0.03) in HFH patients. Urinary excretion of iPF(2 alpha)-III (81+/-10 versus 59+/-4; P<0.05) and iPF(2 alpha)-VI(195+/-18 versus 149+/-20; P<0.05) was also increased in moderately hypercholesterolemic subjects (n=24) compared with their controls. Urinary excretion of iPF(2 alpha)-III and iPF(2 alpha)-VI was correlated (r=0.57; P<0.0001; n=106). LDL iPF(2 alpha)-III levels (ng/mg arachidonate) were elevated (P<0.01) in HFH patients (0.32+/-0.08) compared with controls (0.09+/-0.02). The concentrations of iPF(2)-III in LDL and urine were significantly correlated (r=0.42; P<0.05) in HFH patients. Conclusions-Asymptomatic patients with moderate and severe hypercholesterolemia have evidence of oxidant stress in vivo.

【 授权许可】

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