Plaque rupture induces platelet activation through the liberation of collagen, thrombin, and adenosine 5'-diphosphate (ADP) (Fig. 6). Platelet activation results in an increased surface expression of CD40L, which subsequently is cleaved from the membrane surface. The released sCD40L can activate CD40 on endothelial cells and thereby induce a proinflammatory cascade in the vessel wall. Moreover, sCD40L can activate CD40, which is also expressed on inflammatory cells such as monocytes and T-cells. The subsequent activation of these inflammatory cells and their invasion into the ruptured or eroded plaque results in a further inflammatory perturbation of the vessel wall. In patients with coronary heart disease, sCD40L is primarily released from activated platelets, and subsequently elevated levels have been reported for patients with ACS (Fig. 7) (44,45). Moreover, two studies (37,46) have consistently shown that sCD40L is a powerful biochemical marker of thrombotic inflammatory activation (Fig. 8) in patients with ACS, supporting the close relationship among inflammation, thrombotic activation, and ACSs. Furthermore, both studies have clearly demonstrated that combining this new marker with clas-
Fig. 7. sCD40L levels are primarily released from platelets (A) and are elevated in patients with ACS (B). C, control; SAP, stable angina pectoris; UA, unstable angina; AMI, acute myocardial infarction
Fig. 7. sCD40L levels are primarily released from platelets (A) and are elevated in patients with ACS (B). C, control; SAP, stable angina pectoris; UA, unstable angina; AMI, acute myocardial infarction sic markers of necrosis (troponins) can help to identify patients at the highest risk of subsequent cardiovascular events.
More important, blockade ofthe glycoprotein IIb/IIIa receptor on platelets inhibits the release of sCD40L through inhibition of platelet aggregation via fibrinogen. It has been shown that levels of sCD40L not only identify patients with ACS who are at highest risk
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