Antiinflammatory effects of aspirin in ACS: relevant to its cardio coronary actions?

Thomas Hohlfeld; Karsten Schrör

doi:10.1160/TH15-03-0191

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(03): 469-477
DOI: 10.1160/TH15-03-0191

Theme Issue Article

Schattauer GmbH

Antiinflammatory effects of aspirin in ACS: relevant to its cardio coronary actions?

Authors

Thomas Hohlfeld

¹Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
Karsten Schrör

¹Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

Abstract

Summary

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 salicy-late-related, at low to medium millimolar concentrations and, therefore, are of minor clinical interest. Altogether, there is a wealth of data supporting antiiflammatory effects of aspirin in ACS, but studies generating direct evidence for antiinflammatory effects in ACS remain to be done.

Keywords

Aspirin - platelet pharmacology - thromboxane - inflammatory mediators - thrombin

Full Text

References

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