title: Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.
abstract: BACKGROUND
  Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation.
  
  
  RESULTS
  For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β.
  
  
  CONCLUSIONS
  This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation.
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Padmini
authors.initials: P
authors.lastname: Sirish
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Valeriy
authors.initials: V
authors.lastname: Timofeyev
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Lianguo
authors.initials: L
authors.lastname: Wang
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Kin Sing Stephen
authors.initials: KS
authors.lastname: Lee
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bettaieb
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Sin Mei
authors.initials: SM
authors.lastname: Ma
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Jeong Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Demetria
authors.initials: D
authors.lastname: Su
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Victor C
authors.initials: VC
authors.lastname: Lau
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Richard E
authors.initials: RE
authors.lastname: Myers
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Lieu
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Javier E
authors.initials: JE
authors.lastname: López
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: J Nilas
authors.initials: JN
authors.lastname: Young
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Ebenezer N
authors.initials: EN
authors.lastname: Yamoah
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Fawaz
authors.initials: F
authors.lastname: Haj
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Ripplinger
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.).
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.affiliation: From the Division of Cardiovascular Medicine (P.S., N.L., V.T., X.-D.Z., S.M.M., D.S., V.C.L., R.E.M., D.K.L., J.E.L., N.C.), Department of Pharmacology (L.W., C.M.R.), Department of Entomology and Nematology, Comprehensive Cancer Center (J.Y., K.S.S.L., B.D.H.), Department of Nutrition (A.B., F.H.), and Department of Cardiothoracic Surgery (J.N.Y.), University of California, Davis; Department of Physiology and Cell Biology, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans Affairs, Northern California Health Care System, Mather (N.C.). nchiamvimonvat@ucdavis.edu.
authors.forename: Nipavan
authors.initials: N
authors.lastname: Chiamvimonvat
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D064752:Atrial Remodeling / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors
keywords: animal model; arrhythmia; atrial fibrillation; eicosanoids; inflammation