Surface Expression of P-selectin on Platelets Is Related with Clinical Worsening in Acute Ischemic Stroke

Platelet activation has a critical role in arterial disorders. In this study, we showed that the upregulation of P-selectin expression on platelets was related with clinical worsening in acute ischemic stroke. We serially (within 24 hr, at 72 hr, and 7 days) measured the expression of P-selectin on platelets in patients with acute ischemic stroke (n=45) and investigated the correlation between their extents and clinical severity of ischemic stroke. A significant relationship between the P-selectin expressions and National Institute of Health Stroke Scale (NIHSS) was observed at 72 hr and 7 days after ischemic stroke onset. Patients with clinical deterioration showed significantly increased expression of P-selectin on platelets as compared to those without deterioration. These results suggest that the P-selectin expression on platelets may contribute to the aggravation of clinical course in acute ischemic stroke. Thus, adequate manipulation of activated platelets is an important therapeutic strategy in acute ischemic stroke.

Inhibition of expression of P-selectin by antioxidant in cholesterol-fed rats

Butylated hydroxytoluene (BHT) can inhibit experimental atherosclerosis in animals. Although the agent is an antioxidant, the exact mechanism of the reaction in atherosclerosis is still unknown. To investigate the effects of BHT on expression of P-selectin (PADGEM, GMP-140), intercellular adhesion molecule-1 (ICAM-1) and class II MHC (Ia) antigen, we proposed an experiment on rats. Male rats (n=18 per group) were fed either a normal cholesterol control diet, a normal cholesterol diet containing 0.5% BHT (BD), a high cholesterol diet containing 1.5% cholesterol and 0.1% sodium cholate (CD), or the CD diet containing 0.5% BHT (BCD). Rats were sacrificed after 3 days, and after 1, 2, 4, 10, and 17 weeks of dietary treatment. Although there was no gross or light microscopic atherosclerotic lesions, scanning electron microscopy revealed monocytic adhesion to aortic endothelium and mild endothelial injuries in CD and BCD groups. Immunohistochemically, the addition of BHT to a high cholesterol diet inhibited P-selectin expression but not in ICAM-1 and Ia antigen. These findings suggest that in rats, high cholesterol diets induce expression of ICAM-1, P-selectin and Ia antigen. In addition, the antiatherogenic effect of BHT may play a role in the inhibition of P-selectin.