Modulation of erythrocyte sensitivity to oxidative stress by transient hyperhomocysteinemia in healthy subjects and in patients with coronary artery disease.
BACKGROUND
The pathobiological mechanisms by which Hcy can promote atherothrombosis are not completely understood. Many observations suggest that oxidative consequences of hyperhomocysteinemia have a distinct role in the development of occlusive vascular disease. The aim of this work was to investigate whether sensitivity of erythrocytes to chemically induced oxidative stress in both healthy subjects and patients with clinically ascertained atherosclerosis was modified during the transient increase in homocysteine driven by methionine load.


METHODS
Erythrocyte sensitivity to oxidative stress during transient hyperhomocysteinemia was assessed by cumene hydroperoxide-induced alpha-tocopherol consumption before and after methionine load in 31 healthy subjects and 23 patients with coronary artery disease.


RESULTS
Decreased sensitivity to oxidative challenge ("Type-1" response) after methionine load was more frequent in healthy subjects (35% vs 13% in patients), while increased sensitivity ("Type-2" response) was more frequent in patients (22% vs 6% in healthy subjects). No variation in sensitivity to oxidative challenge throughout the loading test ("Non-variant" response) was detected in either group (58% in healthy subjects and 65% in patients). The distribution of these responses was significantly different between healthy subjects and patients and independent of basal and post-load increase in homocysteine. Plasma lipoperoxides, erythrocyte alpha-tocopherol and glutathione content before methionine load were significantly different between patients and healthy subjects; however only the redox potential of the GSSG/GSH couple was significantly different in the different groups of response.


CONCLUSIONS
The higher frequency of "Type-2" response in patients with respect to healthy subjects suggests that methionine load reveals individual factors that may contribute to the pathogenesis of atherosclerosis.
Vesentini
Nicoletta
N
Istituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche, Via Moruzzi 1, 56124 Pisa, Italy. nvesenti@ifc.cnr.it
Kusmic
Claudia
C
Battaglia
Debora
D
Taddei
Maria Chiara
MC
Barsanti
Laura
L
Parodi
Oberdan
O
Palombo
Carlo
C
Paolicchi
Aldo
A
Barsacchi
Renata
R
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D003324:Coronary Artery Disease / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D024502:alpha-Tocopherol / Q000378:metabolism
D006710:Homocysteine; D008715:Methionine; D024502:alpha-Tocopherol