Increased formation of distinct F2 isoprostanes in hypercholesterolemia.
BACKGROUND
F2 isoprostanes are stable, free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo.


RESULTS
Specific assays were developed by use of mass spectrometry for the F2 isoprostanes iPF2alpha-III and iPF2alpha-VI and arachidonic acid (AA). Urinary excretion of the 2 F2 isoprostanes was significantly increased in hypercholesterolemic patients, whereas substrate AA in urine did not differ between the groups. iPF2alpha-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 iPF2alpha-VI (281+/-22 versus 175+/-13; P<0.0005). Serum cholesterol correlated with urinary iPF2alpha-III (r=0.41; P<0.02) and iPF2alpha-VI (r=0. 39; P<0.03) in HFH patients. Urinary excretion of iPF2alpha-III (81+/-10 versus 59+/-4; P<0.05) and iPF2alpha-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 iPF2alpha-III and iPF2alpha-VI was correlated (r=0.57; P<0.0001; n=106). LDL iPF2alpha-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 iPF2-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.
Reilly
M P
MP
Center for Experimental Therapeutics University of Pennsylvania, Philadelphia, Pa, USA.
Praticò
D
D
Delanty
N
N
DiMinno
G
G
Tremoli
E
E
Rader
D
D
Kapoor
S
S
Rokach
J
J
Lawson
J
J
FitzGerald
G A
GA
D000293:Adolescent; D000328:Adult; D001161:Arteriosclerosis / Q000378:metabolism*; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D028441:F2-Isoprostanes; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008297:Male; D011446:Prospective Studies
D015415:Biomarkers; D028441:F2-Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D002784:Cholesterol; D015237:Dinoprost