Relation between carotid intima-media thickness, platelet surface activation and endothelial cell markers.

Background: The role of platelet activation and endothelial cell damage in the pathogenesis of atherosclerosis was investigated.

Methods: Flow-cytometric detection of platelet activity was accomplished by measuring the surface expression of activated platelet glycoprotein IIb/IIIa (activated CD41) and the lysosomal integral membrane protein (CD63). Levels of thrombomodulin (TM) and von Willebrand factor (vWF) were estimated by the ELISA technique as markers of endothelial cell damage. These procedures were performed in healthy male subjects without obvious signs of atherosclerosis. Also, the intima-media thickness of the carotid artery was measured with high-resolution B- mode ultrasound to quantitate the presence and/or the extent of carotid atherosclerosis.

Results: According to ultrasound findings patients were divided into those with apparent evidence of atherosclerosis (AS+) with intima-media thickness >1.1 mm (n = 19) and those without such evidence (AS-) with intima-media thickness <1.1 mm (n = 17). The percentages of activated CD41 and CD63 surface antigen expression were significantly increased in the AS+ compared to AS- subjects. TM levels were elevated in the former group compared to the latter, while vWF levels were not different in the two groups. Multivariate analysis indicated the independent association of carotid atherosclerosis with each of the expression of activated CD41, CD63 as well as TM levels after adjustment of other risk factors.

Conclusion: This study demonstrates that platelets circulate in an enhanced activation state in asymptomatic atherosclerosis, which is closely related to the degree of endothelial cell damage as expressed by increased plasma levels of TM. The detection of platelet activation can be used as a potential marker for oncoming atherosclerosis.