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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:525.)
© 2003 American Heart Association, Inc.

Editorial

Induction of Platelet-Endothelial Interactions in Postcapillary Venules in Hypercholesterolemia

Critical Role of P-Selectin

Michael C. Berndt

From the Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.

Correspondence to Michael C. Berndt, PhD, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3168, Australia. E-mail Michael.Berndt@med.monash.edu.au

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Hypercholesterolemia is well established as a major risk marker for atherosclerosis and resultant cardiovascular disease. Recent studies suggest that platelets are intimately involved not only in thrombosis after plaque rupture, but also in the earliest events in the atherogenic process.¹ In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Tailor and Granger² establish another potential link between hypercholesterolemia and atherosclerosis by demonstrating that diet-induced hypercholesterolemia promotes P-selectin–dependent platelet-endothelial interactions in postcapillary venules.

See page 675

The adhesive events initiating hemostasis and thrombosis after vessel injury or plaque rupture are now relatively well understood. At shear flow rates relevant to the arterial side of the circulation, initial platelet adhesion involves the coordinated interaction of two platelet adhesion receptors, GP Ib binding to von Willebrand Factor (vWF) and GP VI binding to collagen.^3–5 These adherent platelets become activated, leading to granule release (reflected in surface expression of the -granule membrane glycoprotein, P-selectin) and upregulation of function of the platelet aggregation receptor, the integrin GP IIb-IIIa (_IIbß₃).⁵

In 1995, Wagner and colleagues⁶ demonstrated that platelets not only adhered to vessel matrix, but like leukocytes, could also translocate and stably adhere on activated endothelium in vivo. In their seminal study, the mesenteric venules of mice were acutely activated by treatment with calcium ionophore, A23187. Under these conditions, platelet-endothelial interaction occurred with both resting and activated platelets and, like leukocyte rolling, was critically dependent on the activation-dependent surface expression of endothelial P-selectin. However, at very low shear rates (80 to 100 s^-1. . . [Full Text of this Article]