Platelet activation by collagen is increased in retinal vein occlusion.
Retinal vein occlusion (RVO) is the most common retinal vascular disorder second to diabetic retinopathy. The main risk factors in patients with RVO are hypertension, diabetes, hyperlipidemia, increased blood viscosity and glaucoma. The pathogenesis of RVO has not yet been clarified. In these events platelets could play a very important role. In the present study the platelet response to collagen was deeply investigated. Experiments were carried out on a selected group of RVO patients, which were compared to a group of healthy subjects matched for age, sex, clinical and metabolic characteristics. In resting and activated platelets of both groups of subjects p72syk phosphorylation, phospholipase Cgamma2 phosphorylation, protein kinase C activation, intra-cellular calcium levels and nitric oxide formation were measured. Results show that platelets of patients were more responsive to collagen or ADP than healthy subjects and that the response was significantly different (p < 0.0005) at low concentrations of these agonists. In platelets of patients stimulated with collagen increased phosphorylation of p72syk and phospholipase Cgamma2 was found. Also protein kinase C was more activated in patients. In addition intracellular calcium rise induced by collagen was significantly higher in patients than in healthy subjects. RVO patients showed a lower basal level of nitric oxide both in resting and stimulated platelets compared to healthy subjects. Altogether these results suggest that the platelet hyperaggregability described in patients might be an important factor in the development of RVO contributing to the thrombogenic effects.
Leoncini
Giuliana
G
Department of Experimental Medicine, Biochemistry section, University of Genova, Viale Benedetto XV 1, I-16132 Genova, Italy. leoncini@unige.it
Bruzzese
Debora
D
Signorello
Maria Grazia
MG
Armani
Ugo
U
Piana
Antonietta
A
Ghiglione
Davidina
D
Camicione
Paola
P
D000244:Adenosine Diphosphate; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D003094:Collagen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010979:Platelet Function Tests; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012170:Retinal Vein Occlusion / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D000072377:Syk Kinase; D013997:Time Factors
D047908:Intracellular Signaling Peptides and Proteins; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D003094:Collagen; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D011493:Protein Kinase C; D051966:Phospholipase C gamma; D002118:Calcium