title: Antiinflammatory effects of aspirin in ACS: relevant to its cardiocoronary actions?
abstract: Vascular injury in acute coronary syndromes (ACS) involves a complex cross-talk between inflammatory mediators, platelets and thrombosis, where the interaction between platelets and coagulation factors (e. g. thrombin) is a central link between thrombosis and inflammation. In ACS, aspirin at antiplatelet doses exhibits anti-inflammatory effects as seen from the decrease in inflammation markers such as CRP, M-CSF, MCP-1 and others. These actions probably occur subsequent to inhibition of platelet COX-1-dependent thromboxane formation and its action as a multipotent autocrine and paracrine agent. This likely involves inhibition of thrombin formation as well as inhibition of secondary pro-inflammatory mediators, such as sphingosine-1-phosphate. Experimental and limited clinical data additionally suggest antiinflammatory effects of aspirin independent of its antiplatelet action. For example, aspirin at antiplatelet doses might acetylate COX-2 in vascular cells, directing the activity of the enzyme into a 15-lipoxygenase which by transcellular metabolism results in the formation of 15-epi-lipoxin (´aspirin-triggered lipoxin´), an antiinflammatory mediator. Furthermore, aspirin stimulates eNOS via lysine-acetylation, eventually resulting in induction of heme oxygenase (HO-1), which improves the antioxidative potential of vascular cells. All of these effects have been seen at antiplatelet doses of 100-300 mg/day, equivalent to peak plasma levels of 10-30 µM. Many more potentially antiinflammatory mechanisms of aspirin have been described, mostly salicylate-related, at low to medium millimolar concentrations and, therefore, are of minor clinical interest. Altogether, there is a wealth of data supporting anti-inflammatory effects of aspirin in ACS, but studies generating direct evidence for antiinflammatory effects in ACS remain to be done.
authors.affiliation: Prof. Dr. med. Thomas Hohlfeld, Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany, Tel.: +49 211 81 12505, Fax: +49 211 81 14781, E-mail: hohlfeld@uni-duesseldorf.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hohlfeld
authors.forename: Karsten
authors.initials: K
authors.lastname: Schrör
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013917:Thrombin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D010975:Platelet Aggregation Inhibitors; D013917:Thrombin
keywords: Aspirin; inflammatory mediators; platelet pharmacology; thrombin; thromboxane