Increased tyrosine phosphorylation of platelet proteins including pp125(FAK) suggests endogenous activation and aggregation in pulmonary hypertension.
Despite of several lines of evidence indicating a pathophysiologic role of platelets in pulmonary hypertension, the occurrence of chronic endogenous platelet activation has been a matter of debate. It was hypothesized that the pattern of tyrosine phosphorylation of platelet proteins examined ex vivo could provide information on the state of platelet activation. This was examined in 10 patients with pulmonary arterial hypertension aged 18 to 53 years. Phosphotyrosine density and the amounts of specific proteins were analyzed in resting platelets after reaction with anti-phosphotyrosine, anti-pp60(s-src), anti-pp125(FAK), and anti-alphaIIbbeta3 antibodies. There was a 79% increase in protein-associated phosphotyrosine in patients in comparison to levels in controls (p<0.05). In particular, phosphorylation on tyrosine residues of pp120 and pp125(FAK) increased 24% and 57%, respectively (p<0.05). Although pp60(s-src)-associated phosphotyrosine was not altered in the patient group as a whole, it was clearly decreased in three subjects. Platelet content of beta3 integrin, pp60(s-src), and pp125(FAK), was not altered. This pattern of phosphorylation suggests an ongoing process of platelet activation. Because phosphorylation of pp125(FAK) is a late, integrin-dependent event, results suggest that platelet activation and aggregation occur in vivo in these patients.
Maeda
Nair Y
NY
Pró-Sangue Foundation, Heart Institute, School of Medicine, University of São Paulo, Brazil. nanamaeda@uol.com.br
Bydlowski
Sergio P
SP
Lopes
Antonio A
AA
D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D015539:Platelet Activation; D010974:Platelet Aggregation
D019000:Phosphotyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases