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: 2.21). 02/2011; 35(1):98-113. DOI: 10.1007/s10753-011-9294-8
Source: PubMed


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.

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Available from: Simon Gelman, Mar 17, 2014
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    • "Also, high levels of lipoxins and resolvins were recently identified in human breast milk (Weiss et al. 2013) as well as in animal placenta (Jones et al. 2013). These findings raise important new farreaching implications for whether SPMs can play roles in cell traffic associated with organ development as well as regulate acute inflammatory responses around surgical events and tissue regeneration (Pillai et al. 2012; Dalli et al. 2013b). "
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    Full-text · Article · Oct 2014 · Cold Spring Harbor perspectives in biology
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    • "These signaling networks further delineate that resolution actively begins with initiation of inflammation (Serhan and Savill, 2005). Moreover, they provide a molecular basis for delayed resolvers and nonresolving phenotypes in humans (Morris et al., 2010; Pillai et al., 2012). SPM local production and action on leukocyte trafficking and function, as well as miRNA regulation , can exert sustained tissue alterations that permit return to homeostasis. "
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    Full-text · Article · Nov 2013 · Immunity
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    • "Due to its chemotactic properties, 12-HETE has been linked to healing processes during inflammation [58, 59]. Analysis of oxylipin profiles after abdominal aortic aneurism repair also showed high levels of 12-HETE in plasma 24 h after surgery for the group of patients which were in the resolution phase of inflammation [60]. "
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    ABSTRACT: Oxylipins, including eicosanoids, affect a broad range of biological processes, such as the initiation and resolution of inflammation. These compounds, also referred to as lipid mediators, are (non-) enzymatically generated by oxidation of polyunsaturated fatty acids such as arachidonic acid (AA). A plethora of lipid mediators exist which makes the development of generic analytical methods challenging. Here we developed a robust and sensitive targeted analysis platform for oxylipins and applied it in a biological setting, using high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) operated in dynamic multiple reaction monitoring (dMRM). Besides the well-described AA metabolites, oxylipins derived from linoleic acid, dihomo-γ-linolenic acid, α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid were included. Our comprehensive platform allows the quantitative evaluation of approximately 100 oxylipins down to low nanomolar levels. Applicability of the analytical platform was demonstrated by analyzing plasma samples of patients undergoing cardiac surgery. Altered levels of some of the oxylipins, especially in certain monohydroxy fatty acids such as 12-HETE and 12-HEPE, were observed in samples collected before and 24 h after cardiac surgery. These findings indicate that this generic oxylipin profiling platform can be applied broadly to study these highly bioactive compounds in relation to human disease. Figure LC-MS/MS chromatogram of 104 oxylipins on a Triple Quadrupole MS system employing dynamic MRM in the Negative Ion Electrospray mode Electronic supplementary material The online version of this article (doi:10.1007/s00216-012-6226-x) contains supplementary material, which is available to authorized users.
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