P044
Associations of the redox state of cysteine-34 of human
albumin with age, kidney function and vascular health
Brigitte M. Winklhofer-Roob1, Karl Oettl2,
Gernot Faustmann1, Theopisti Maimari2,
Hildegard Hafner-Giessauf2, Beate Tiran2,
Alexander R. Rosenkranz2 and Johannes M. Roob2
1
Karl-Franzens University of Graz, Graz, Austria
2
Medical University of Graz, Graz, Austria
Background: The goal of the FP7-project BIOCLAIMS is to identify
biomarkers of metabolic robustness and health. Albumin, a human
plasma protein, is abundantly present in the circulation and highly
susceptible to oxidative modification.
Subjects and Methods: After an overnight fast, 784 healthy volunteers
and patients with impaired renal function were studied for vascular
status (flow-mediated dilatation, FMD; intima-media thickness, IMT),
kidney function (estimated glomerular filtration rate, eGFR-MDRD),
vitamin C status, and 3 fractions of human albumin, based on the
redox state of cysteine-34: non-oxidized mercaptalbumin containing
a free thiol group (HMA), reversibly oxidized non-mercaptalbumin-1
containing a disulfide (HNA-1), and irreversibly oxidized non-mercaptalbumin-2 containing a sulfinic or sulfonic acid group (HNA2), by
HPLC with fluorescence detection (Methods Enzymol 2010;474:181).
Results: HMA decreased with decreasing eGFR (r=0.639), while
HNA1 showed the opposite (r=0.637). FMD (% change after ischemia)
was positively associated with HMA (r=0.445) and inversely with
HNA1 (r=0,447), while IMT increased with decreasing HMA (r=0.529)
and with increasing HNA1 (r=-0,529). HMA decreased (r=0.622), while
HNA1 increased (r=0.628) with age. Plasma ascorbate concentrations
were positively associated with HMA (r=0.277) and inversely with
HNA1 (r=0.288). All P-values <0.001. Changes in HNA2 were small,
but still statistically significant for eGFR and age.
Conclusions: The redox state of albumin is associated with age,
vitamin C status, kidney function and vascular function/status
and could serve as a biomarker of the capacity to cope with
oxidative stress.