title: New perspectives on aspirin and the endogenous control of acute inflammatory resolution.
abstract: Aspirin is unique among the nonsteroidal anti-inflammatory drugs in that it has both anti-inflammatory as well as cardio-protective properties. The cardio-protective properties arise form its judicious inhibition of platelet-derived thromboxane A2 over prostacyclin, while its anti-inflammatory effects of aspirin stem from its well-established inhibition of prostaglandin (PG) synthesis within inflamed tissues. Thus aspirin and the other NSAIDs have popularised the notion of inhibiting PG biosynthesis as a common anti-inflammatory strategy based on the erroneous premise that all eicosanoids are generally detrimental to inflammation. However, our fascination with aspirin has shown a more affable side to lipid mediators based on our increasing interest in the endogenous control of acute inflammation and in factors that mediate its resolution. Epi-lipoxins (epi-LXs), for instance, are produced from aspirin's acetylation of inducible cyclooxygenase 2 (COX-2) and together with Resolvins represent an increasingly important family of immuno-regulatory and potentially cardio-protective lipid mediators. Aspirin is beginning to teach us what nature knew all along--that not all lipid mediators are bad. It seems that while some eicosanoids are pathogenic in a variety of diseases, others are unarguable protective. In this review we will re-count aspirin's colorful history, discuss its traditional mode of action and the controversies associated therewith, as well as highlight some of the new pathways in inflammation and the cardiovascular systems that aspirin has recently revealed.
authors.affiliation: Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, 5 University Street, University College London, London WC1E 6JJ, UK.
authors.forename: Thea
authors.initials: T
authors.lastname: Morris
authors.forename: Melanie
authors.initials: M
authors.lastname: Stables
authors.forename: Derek W
authors.initials: DW
authors.lastname: Gilroy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D015525:Fatty Acids, Omega-3 / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007962:Leukocytes / Q000502:physiology; D044045:Lipoxins / Q000502:physiology; D008084:Lipoxygenase / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000502:physiology; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015525:Fatty Acids, Omega-3; C509871:HSH2 protein, mouse; D044045:Lipoxins; D018336:Receptors, Aryl Hydrocarbon; D004281:Docosahexaenoic Acids; D009569:Nitric Oxide; D015118:Eicosapentaenoic Acid; D008084:Lipoxygenase; D001241:Aspirin