The intimate connection between coagulation and inflammation in the pathogenesis of vascular disease has moved more and more into focus of clinical research. This paper focuses on the essential components of this interplay in the settings of cardiovascular disease and acute coronary syndrome. Tissue factor, the main initiator of the extrinsic coagulation pathway, plays a central role via causing a proinflammatory response through activation of coagulation factors and thereby initiating coagulation and downstream cellular signalling pathways. Regarding activated clotting factors II, X, and VII, protease-activated receptors provide the molecular link between coagulation and inflammation. Hereby, PAR-1 displays deleterious as well as beneficial properties. Unravelling these interrelations may help developing new strategies to ameliorate the detrimental reciprocal aggravation of inflammation and coagulation. 1. Introduction Systemic and local proinflammatory changes are in focus when investigating the pathophysiology of arteriosclerosis and acute coronary syndromes. In acute myocardial infarction (AMI), proinflammatory markers such as C-reactive protein (CRP), interleukins, or monocyte-chemoattractant protein (MCP)-1 are elevated [1–3] and their increase is of prognostic relevance for future cardiovascular events [4–6] and mortality [7–9]. Moreover, in healthy persons elevated proinflammatory markers are associated with an increase in cardiovascular risk [10–12]. Patients with increased circulating proinflammatory markers in AMI present with decreased myocardial salvage after coronary reperfusion therapy [13]. Similarly, in experimental studies, high levels of CRP deteriorate infarct size [14]. Sources of inflammatory response are vascular cells such as activated endothelial cells, which release proinflammatory cytokines such as interleukin (IL)-8 [15]. IL-8 is a CXC cytokine that acts as a chemoattractant and agonist for neutrophils, lymphocytes, and monocytes and is found in macrophage-rich atherosclerotic plaques [16]. Under flow conditions, IL-8 facilitates the arrest of monocytes on endothelium [16], which is necessary for migration into the intima in evolution of arteriosclerosis. Reperfusion injury after AMI as well as systemic inflammatory response syndrome can be associated to increased levels of IL-8 [17]. In experimental setting, murine IL-8 receptor knock-out mice display smaller arteriosclerotic lesions with less macrophages [18]. Apart from their contribution to arteriosclerosis, CXC cytokines are also produced by malignant cells and can
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