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.

journal_name

Thromb Haemost

authors

Hohlfeld T,Schrör K

doi

10.1160/TH15-03-0191

subject

Has Abstract

pub_date

2015-08-31 00:00:00

pages

469-77

issue

3

eissn

0340-6245

issn

2567-689X

pii

15-03-0191

journal_volume

114

pub_type

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