Chemical mediators of inflammation and resolution in post-operative abdominal aortic aneurysm patients.

Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Inflammation (Impact Factor: 1.92). 02/2011; 35(1):98-113. DOI: 10.1007/s10753-011-9294-8
Source: PubMed

ABSTRACT Temporal-metabolomic studies of local mediators during inflammation and its resolution uncovered novel pathways and mediators, e.g., lipoxins, resolvins, and protectins that stimulate key resolution responses. Since these studies were carried out with isolated human cells and in animal models, it is important to determine in humans whether temporal profiles between pro-inflammatory mediators and pro-resolving mediators are demonstrable in vivo. To this end, we examined patients undergoing abdominal aortic aneurysm (AAA) surgery. Profiles of mediators including eicosanoids were assessed in addition to pro-resolving mediators. The results demonstrate temporal relationships for local-acting peptides (e.g., VEGF, IL-10, TGF(β)) and lipid mediators (leukotrienes and resolvins). In addition, profiles obtained for AAA patients divided into two groups based on their temporal profile: one group consistent with a pro-inflammatory and another with a resolving profile. Together, these translational metabolomic profiles demonstrate for the first time the temporal relationships between local mediators in humans relevant in inflammation resolution.

Download full-text


Available from: Simon Gelman, Mar 17, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mounting of the acute inflammatory response is crucial for host defense and pivotal to the development of chronic inflammation, fibrosis, or abscess formation versus the protective response and the need of the host tissues to return to homeostasis. Within self-limited acute inflammatory exudates, novel families of lipid mediators are identified, named resolvins (Rv), protectins, and maresins, which actively stimulate cardinal signs of resolution, namely, cessation of leukocytic infiltration, counterregulation of proinflammatory mediators, and the uptake of apoptotic neutrophils and cellular debris. The biosynthesis of these resolution-phase mediators in sensu stricto is initiated during lipid-mediator class switching, in which the classic initiators of acute inflammation, prostaglandins and leukotrienes (LTs), switch to produce specialized proresolving mediators (SPMs). In this work, we review recent evidence on the structure and functional roles of these novel lipid mediators of resolution. Together, these show that leukocyte trafficking and temporal spatial signals govern the resolution of self-limited inflammation and stimulate homeostasis.
    Cold Spring Harbor perspectives in biology 10/2014; 7(2). DOI:10.1101/cshperspect.a016311 · 8.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular disease is an inflammatory process and the leading cause of death in the United States. Novel omega-3 derived potent lipid mediators, termed resolvins and protectins, have been identified as major pathophysiologic players in the resolution phase of the inflammatory response. Potent lipid mediators offer tremendous metabolic and pathophysiologic insights in regard to the risk and treatment of cardiovascular disease. In this review, resolvins and protectins are described and analyzed as accelerators of discovery via their potential role as biomarkers for research and clinical decision making in cardiovascular disease. Specific barriers relating to biomarker validation, laboratory methods, and improvement of risk models are introduced and discussed. Potential therapeutic impacts in cardiovascular disease are also mentioned with special consideration for cost-saving implications with respect to dietary fish oil as an alternative to resolvin and protectin treatment. Given the high tolerability of fish oil supplements and previously described benefits of omega-3 fatty acid intake in cardiovascular disease, we conclude that resolvins and protectins are set to soon take center stage as future biomarkers and well-tolerated therapies for cardiovascular disease.
    02/2012; 2(1).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Resolvin D1 (RvD1) limits neutrophil recruitment during acute inflammation and is derived from omega-3 docosahexaenoic acid to promote catabasis. The contribution of its specific receptors, the lipoxin A(4)/Annexin-A1 receptor formyl-peptide receptor 2 (FPR2/ALX) and the orphan receptor G-protein-coupled receptor 32 (GPR32) are of considerable interest. RvD1 reduced human polymorphonuclear leukocytes recruitment to endothelial cells under shear conditions as quantified using a flow chamber system. Receptor-specific antibodies blocked these anti-inflammatory actions of RvD1, with low (1 nmol/L) concentrations sensitive to GPR32 blockade, while the higher (10 nmol/L) concentration appeared FPR2/ALX-specific. Interestingly, polymorphonuclear leukocytes surface expression of FPR2/ALX but not GPR32 increased following activation with pro-inflammatory stimuli, corresponding with secretory vesicle mobilization. Lipid mediator metabololipidomics carried out with 24-hour exudates revealed that RvD1 in vivo gave a significant reduction in the levels of a number of pro-inflammatory mediators including prostaglandins and leukotriene B(4). These actions of RvD1 were abolished in fpr2 null mice. Pro-resolving lipid mediators and their receptors, such as RvD1 and the 2 G-protein-coupled receptors, studied here regulate resolution and may provide new therapeutic strategies for diseases with a vascular inflammatory component.
    Arteriosclerosis Thrombosis and Vascular Biology 04/2012; 32(8):1970-8. DOI:10.1161/ATVBAHA.112.249508 · 5.53 Impact Factor