Platelet P-Selectin Expression Is Associated With Atherosclerotic Wall Thickness in Carotid Artery in Humans

Abstract

Background-Recent genetic animal models reveal important roles of platelet P-selectin on progression of atherosclerosis.In the present study, we examine the relation between platelet P-selectin expression and atherosclerotic parameters in 517 subjects. Methods and Results-Unrelated subjects (nϭ517; 235 male and 282 female), including 187 with type 2 diabetes, 184with hypertension, and 366 with hyperlipidemia, were enrolled in the study. P-selectin expression was determined by whole-blood flow cytometry. Arterial stiffness (stiffness index ␤) and arterial wall thickness (intima-media thickness [IMT]) were determined by carotid ultrasound. P-selectin expression was significantly and positively correlated with carotid IMT and stiffness index ␤. Multiple regression analyses showed that the association of the percentage of P-selectin-positive platelets with carotid IMT was independent of other clinical factors. Moreover, the percentage of P-selectin-positive platelets was higher in subjects with carotid plaque and was an independent factor associated with occurrence of carotid plaque analyzed by multiple logistic regression analysis. Finally, the percentage of P-selectinpositive platelets was positively associated with age, body mass index, systolic and diastolic blood pressure, and HbA1c and inversely associated with HDL cholesterol. Conclusions-Platelet P-selectin is independently associated with atherosclerotic arterial wall changes in human subjects.(Circulation. 2003;108:524-529.)

Platelet-Monocyte Aggregates are Independently Associated with Occurrence of Carotid Plaques in Type 2 Diabetic Patients

“…We have also found in a human study that the expression of P-selectin on platelets is positively associated with the thickness of the atherosclerotic wall in the carotid artery (21). These findings suggest that activated platelets play crucial roles in the progression of spontaneous atherosclerosis as well as arterial thrombosis.…”

“…The expression of P-selectin has been considered a good marker of platelet activation, since P-selectin translocates to the surface of the plasmatic membrane from the α-granule membrane upon platelet activation. Increased percentages of P-selectin-positive platelets in diabetic patients have been reported by several groups including ours (19)(20)(21). It has been proposed that platelet-monocyte aggregates may be a more sensitive marker of platelet activation than platelet P-selectin expression, since degranulated platelets rapidly lose surface P-selectin in vivo (22,23).…”

“…All antibodies were purchased from Beckman Coulter, Inc. The level of P-selectin expressed on platelets was determined as described previously (21).…”

“…In brief, each subject was examined in the supine position, and the examination included the carotid bulb and 4 cm of the right common carotid artery. Both the near and far walls of these arterial segments were scanned longitudinally and transversely to assess the occurrence of plaques, which were defined as localized echo structures that encroached into the vessel lumen and for which the distance between the media-adventitia interface and the lesion surface facing the lumen was ≥ 1 mm (21,28).…”

Correlation Study of Pulmonary Embolism and High‐density Lipoprotein Cholesterol

“…In the meantime, HDL could boost the production of eNOS in endothelial cells so as to further increase the release of nitric oxide (NO) and enhance the bioavailability of NO. 16 extrinsic pathway of blood coagulation-tissue factor 19,20 and suppress the activity of clotting factors, Va and VIIIa. 21 Animal experiments have confirmed that HDL could inhibit the in vivo activity of platelets both directly and indirectly.…”