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Although medical prevention and treatment of atherothrombotic disease can be effective to some extent, it is far from ideal, and novel treatment strategies are desperately needed. One of the reasons why medical treatment is only partly effective is related to the fact that atherothrombotic disease is a complex disorder and, despite recent advances, our understanding of the highly sophisticated interactions among endothelial dyspictures of swallow tattoos, inflammation, thrombosis, and insulin resistance remains limited. Therefore, future work is needed to disentangle these interactions, which would enable us to understand the pathogenesis of the disease and to construct more effective treatment strategies. Acknowledgment R. A. Ajjan is funded by a Clinician Scientist Award from the Department of Health, United Kingdom. References 1. Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet Med 1997;14(suppl 5):S1–S85. 2. Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for diabetes mellitus in the United States. JAMA 2003;290(14):1884–1890. TABLE 135. 2. Antithrombotic properties of agents commonly used in the prevention and treatment of atherothrombotic conditions Agent Antiatherosclerotic effect Antithrombotic effect Aspirin ? Mild antiinflammatory effect Inhibition of COX-1 (v platelet activation) Acetylation of fibrinogen (less porous fibrin network and increased ) Clopidogrel ? Inactivation of ADP receptor (v platelet activation) ? v Fibrinogen ACEI/ARB Improvement in EC pictures of swallow tattoos Improvement in EC pictures of swallow tattoos (? v platelet activation) v Oxidative stress v TF (v thrombus formation) v PAI-1, ? ^ t-PA (improved ) Beta-blockers Improvement in EC pictures of swallow tattoos ^ NO (v platelet activation) v PAI-1 (^ ) CCB v Oxidative stress ^ NO (v platelet activation) v VSMC proliferation and migration v Apoptosis Statins Improvement in EC pictures of swallow tattoos v TF, ^ TM, v FVII activity, v FV, v FXIII activation v Oxidative stress (v thrombus formation) v Inflammation and switching to v PAI-1 (^ ) Th2 cytokine response Favorable effect on lipid profile PPAR? Improvement in EC pictures of swallow tattoos v TF, v fibrinogen (v thrombus formation) v Th1 cytokine production v PAI-1 (^ ) Efflux of cholesterol from cells Favorable effect on lipid profile PPAR? Improvement in EC pictures of swallow tattoos ^ NO (v platelet aggregation) Switching to Th2 cytokine production v PAI-1 (^ ) Efflux of cholesterol from cells v sCD40L v CRP Metformin Improvement in EC pictures of swallow tattoos v VII, v XIII cross-linking, v clot polymerization v Oxidative stress (v thrombus formation) v Adhesion molecule expression v PAI-1, possible interference with clot structure (^ ) ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; PPAR: peroxisome proliferator activated receptor.


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