Homocysteine-induced inhibition of nitric oxide production in platelets: a study on healthy and diabetic subjects.
OBJECTIVE
The molecular mechanisms involved in the platelet activation observed in hyperhomocysteinemia are not known. We aimed to discover if homocysteine concentrations are associated with abnormal platelet nitric oxide production in healthy and diabetic subjects.


METHODS
The study cohort included 28 patients with Type I (insulin-dependent) diabetes mellitus, 30 patients with Type II (non-insulin-dependent) diabetes mellitus, and 34 healthy subjects. Homocysteine plasma concentrations were measured by high-performance liquid chromatography. Platelet nitric oxide production was measured using a nitric oxide meter before and after a 3-h incubation with 100 micromol/l homocysteine. Stimulation experiments were done in vitro by the addition of alpha-thrombin (0.2 U/ml).


RESULTS
Basal platelet nitric oxide production was lower in diabetic patients than in healthy subjects. Nitric oxide release was reduced by in vitro homocysteine incubation, being lower in platelets from diabetic patients than in platelets from control subjects. Thrombin increased nitric oxide synthesis in platelets from healthy subjects both in the presence and absence of homocysteine. In diabetic subjects thrombin increased nitric oxide release in the absence of homocysteine. But in the presence of homocysteine the response was reduced. An inverse relation was found between plasma homocysteine levels and basal platelet nitric oxide release in diabetic and healthy subjects.


CONCLUSIONS
Homocysteine could exert its atherogenic action in healthy and diabetic subjects partly by inhibiting platelet nitric oxide production with the subsequent increased platelet activation and aggregation.
Mutus
B
B
Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada.
Rabini
R A
RA
Staffolani
R
R
Ricciotti
R
R
Fumelli
P
P
Moretti
N
N
Martarelli
D
D
Mazzanti
L
L
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology
D006710:Homocysteine; D009569:Nitric Oxide; D013917:Thrombin