title: Arachidonic acid-derived signaling lipids and functions in impaired healing.
abstract: Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT(-/-) mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs. The latter suggests excess coagulation and potentially increased platelet aggregation. We show here that in these impaired wounds there is an imbalance in the arachidonic acid (AA) derived eicosonoids that mediate or modulate inflammatory reactions and platelet aggregation. In the LIGHT(-/-) impaired wounds there is a significant increase in enzymatically derived breakdown products of AA. We found that early after injury there was a significant increase in the eicosanoids 11-, 12-, and 15-hydroxyeicosa-tetranoic acid, and the proinflammatory leukotrienes (LTD4 and LTE) and prostaglandins (PGE2 and PGF2α ). Some of these eicosanoids also promote platelet aggregation. This led us to examine the levels of other eicosanoids known to be involved in the latter process. We found that thromboxane (TXA2 /B2 ), and prostacyclins 6kPGF1α are elevated shortly after wounding and in some cases during healing. To determine whether they have an impact in platelet aggregation and hemostasis, we tested LIGHT(-/-) mouse wounds for these two parameters and found that, indeed, platelet aggregation and hemostasis are enhanced in these mice when compared with the control C57BL/6 mice. Understanding lipid signaling in impaired wounds can potentially lead to development of new therapeutics or in using existing nonsteroidal anti-inflammatory agents to help correct the course of healing.
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California.|Department of Bioengineering Interdepartmental Graduate Program, University of California, Riverside, California.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dhall
authors.affiliation: Department of Surgery, Virginia Commonwealth University, Richmond, Virginia.|Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, Virginia.|The Massey Cancer Center, Richmond, VA, Virginia Commonwealth University, Richmond, Virginia.|Virginia Commonwealth University Reanimation Engineering Science Center (VCURES).
authors.forename: Dayanjan Shanaka
authors.identifier: http://orcid.org/0000-0002-2124-5109
authors.initials: DS
authors.lastname: Wijesinghe
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Zubair A
authors.initials: ZA
authors.lastname: Karim
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California.
authors.forename: Anthony
authors.initials: A
authors.lastname: Castro
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California.
authors.forename: Hari Priya
authors.initials: HP
authors.lastname: Vemana
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Fadi T
authors.initials: FT
authors.lastname: Khasawneh
authors.affiliation: Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, Virginia.|The Massey Cancer Center, Richmond, VA, Virginia Commonwealth University, Richmond, Virginia.|Virginia Commonwealth University Reanimation Engineering Science Center (VCURES).|Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Chalfant
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside, California.|Department of Bioengineering Interdepartmental Graduate Program, University of California, Riverside, California.
authors.forename: Manuela
authors.initials: M
authors.lastname: Martins-Green
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D050356:Lipid Metabolism / Q000187:drug effects*; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010196:Pancreatic Elastase / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D013552:Swine; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D016718:Arachidonic Acid; D010196:Pancreatic Elastase