Regulation of microvascular thromboembolism in vivo

Atherothrombosis and embolization are main causes of morbidity and mortality in the Western world. To optimize treatment, better understanding of the factors involved in thromboembolism in vivo is needed. The course and outcome of a thromboembolic process are determined by the local balance between anti and prothrombotic factors. In healthy vessels, endothelial antithrombotic properties prevent blood platelets from interacting with the vessel wall. Upon vessel wall damage or endothelial activation, however, prothrombotic factors temporarily overrule the antithrombotic factors, leading to thrombus formation and embolization. According to this concept, thromboembolism ends when the balance is restored. Animal models on microvascular thromboembolism have provided evidence that the endothelium is eminently involved in the regulation of thromboembolism, and that shear forces are an important determinant of endothelial function. Therefore, in this review focus is on the endothelial regulation of platelet-vessel wall interactions during thromboembolism in vivo. Anti- and prothrombotic properties of vascular endothelium will be discussed, paying special attention to the endothelium-derived platelet inhibiting substances nitiric oxide (NO) and prostacyclin (PGl(2)) and to differences between arteriolar and venular endothelium. In addition, the involvement of shear forces in microvascular thromboembolic processes in vivo will be described