PMID- 29437834
OWN - NLM
STAT- In-Data-Review
LR  - 20190329
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 122
IP  - 6
DP  - 2018 Mar 16
TI  - Impaired Production and Diurnal Regulation of Vascular RvDn-3 DPA Increase
      Systemic Inflammation and Cardiovascular Disease.
PG  - 855-863
LID - 10.1161/CIRCRESAHA.117.312472 [doi]
AB  - RATIONALE: Diurnal mechanisms are central to regulating host responses. Recent
      studies uncovered a novel family of mediators termed as specialized proresolving 
      mediators that terminate inflammation without interfering with the immune
      response. OBJECTIVE: Herein, we investigated the diurnal regulation of
      specialized proresolving mediators in humans and their role in controlling
      peripheral blood leukocyte and platelet activation. METHODS AND RESULTS: Using
      lipid mediator profiling and healthy volunteers, we found that plasma
      concentrations of n-3 docosapentaenoic acid-derived D-series resolvins (RvDn-3
      DPA) were regulated in a diurnal manner. The production and regulation of these
      mediators was markedly altered in patients at risk of myocardial infarct. These
      changes were associated with decreased 5-lipoxygenase expression and activity, as
      well as increased systemic adenosine concentrations. We also found a significant 
      negative correlation between plasma RvDn-3 DPA and markers of platelet, monocyte,
      and neutrophil activation, including CD63 and CD11b. Incubation of RvDn-3 DPA
      with peripheral blood from healthy volunteers and patients with cardiovascular
      disease significantly and dose-dependently decreased platelet and leukocyte
      activation. Furthermore, administration of RvD5n-3 DPA to ApoE(-/-)
      (apolipoprotein E deficient) mice significantly reduced platelet-leukocyte
      aggregates, vascular thromboxane B2 concentrations, and aortic lesions.
      CONCLUSIONS: These results demonstrate that peripheral blood RvDn-3 DPA are
      diurnally regulated in humans, and dysregulation in the production of these
      mediators may lead to cardiovascular disease.
CI  - (c) 2018 The Authors.
FAU - Colas, Romain A
AU  - Colas RA
AD  - From the Lipid Mediator Unit, William Harvey Research Institute (R.A.C., P.R.S., 
      M.E.W., R.M.M., J.D.) NIHR Cardiovascular Biomedical Research Unit at Barts
      (M.B.), and the Centre for Inflammation and Therapeutic Innovation (J.D.), Barts 
      and the London School of Medicine and Dentistry, Queen Mary University of London,
      United Kingdom; School of Biochemistry and Immunology, Trinity Biomedical
      Sciences Institute, Trinity College Dublin, Ireland (Z.Z.); and Department of
      Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin
      (A.M.C.).
FAU - Souza, Patricia R
AU  - Souza PR
AD  - From the Lipid Mediator Unit, William Harvey Research Institute (R.A.C., P.R.S., 
      M.E.W., R.M.M., J.D.) NIHR Cardiovascular Biomedical Research Unit at Barts
      (M.B.), and the Centre for Inflammation and Therapeutic Innovation (J.D.), Barts 
      and the London School of Medicine and Dentistry, Queen Mary University of London,
      United Kingdom; School of Biochemistry and Immunology, Trinity Biomedical
      Sciences Institute, Trinity College Dublin, Ireland (Z.Z.); and Department of
      Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin
      (A.M.C.).
FAU - Walker, Mary E
AU  - Walker ME
AD  - From the Lipid Mediator Unit, William Harvey Research Institute (R.A.C., P.R.S., 
      M.E.W., R.M.M., J.D.) NIHR Cardiovascular Biomedical Research Unit at Barts
      (M.B.), and the Centre for Inflammation and Therapeutic Innovation (J.D.), Barts 
      and the London School of Medicine and Dentistry, Queen Mary University of London,
      United Kingdom; School of Biochemistry and Immunology, Trinity Biomedical
      Sciences Institute, Trinity College Dublin, Ireland (Z.Z.); and Department of
      Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin
      (A.M.C.).
FAU - Burton, Maudrian
AU  - Burton M
AD  - From the Lipid Mediator Unit, William Harvey Research Institute (R.A.C., P.R.S., 
      M.E.W., R.M.M., J.D.) NIHR Cardiovascular Biomedical Research Unit at Barts
      (M.B.), and the Centre for Inflammation and Therapeutic Innovation (J.D.), Barts 
      and the London School of Medicine and Dentistry, Queen Mary University of London,
      United Kingdom; School of Biochemistry and Immunology, Trinity Biomedical
      Sciences Institute, Trinity College Dublin, Ireland (Z.Z.); and Department of
      Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin
      (A.M.C.).
FAU - Zaslona, Zbigniew
AU  - Zaslona Z
AD  - From the Lipid Mediator Unit, William Harvey Research Institute (R.A.C., P.R.S., 
      M.E.W., R.M.M., J.D.) NIHR Cardiovascular Biomedical Research Unit at Barts
      (M.B.), and the Centre for Inflammation and Therapeutic Innovation (J.D.), Barts 
      and the London School of Medicine and Dentistry, Queen Mary University of London,
      United Kingdom; School of Biochemistry and Immunology, Trinity Biomedical
      Sciences Institute, Trinity College Dublin, Ireland (Z.Z.); and Department of
      Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin
      (A.M.C.).
FAU - Curtis, Annie M
AU  - Curtis AM
AD  - From the Lipid Mediator Unit, William Harvey Research Institute (R.A.C., P.R.S., 
      M.E.W., R.M.M., J.D.) NIHR Cardiovascular Biomedical Research Unit at Barts
      (M.B.), and the Centre for Inflammation and Therapeutic Innovation (J.D.), Barts 
      and the London School of Medicine and Dentistry, Queen Mary University of London,
      United Kingdom; School of Biochemistry and Immunology, Trinity Biomedical
      Sciences Institute, Trinity College Dublin, Ireland (Z.Z.); and Department of
      Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin
      (A.M.C.).
FAU - Marques, Raquel M
AU  - Marques RM
AD  - From the Lipid Mediator Unit, William Harvey Research Institute (R.A.C., P.R.S., 
      M.E.W., R.M.M., J.D.) NIHR Cardiovascular Biomedical Research Unit at Barts
      (M.B.), and the Centre for Inflammation and Therapeutic Innovation (J.D.), Barts 
      and the London School of Medicine and Dentistry, Queen Mary University of London,
      United Kingdom; School of Biochemistry and Immunology, Trinity Biomedical
      Sciences Institute, Trinity College Dublin, Ireland (Z.Z.); and Department of
      Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin
      (A.M.C.).
FAU - Dalli, Jesmond
AU  - Dalli J
AD  - From the Lipid Mediator Unit, William Harvey Research Institute (R.A.C., P.R.S., 
      M.E.W., R.M.M., J.D.) NIHR Cardiovascular Biomedical Research Unit at Barts
      (M.B.), and the Centre for Inflammation and Therapeutic Innovation (J.D.), Barts 
      and the London School of Medicine and Dentistry, Queen Mary University of London,
      United Kingdom; School of Biochemistry and Immunology, Trinity Biomedical
      Sciences Institute, Trinity College Dublin, Ireland (Z.Z.); and Department of
      Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin
      (A.M.C.). j.dalli@qmul.ac.uk.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - 107613/Wellcome Trust/United Kingdom
GR  - 677542/European Research Council/International
PT  - Journal Article
DEP - 20180205
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
PMC - PMC5924694
MID - EMS76098
OTO - NOTNLM
OT  - adenosine
OT  - eicosanoids
OT  - lipoxygenase
OT  - monocyte
OT  - neutrophils
OT  - platelets
EDAT- 2018/02/14 06:00
MHDA- 2018/02/14 06:00
CRDT- 2018/02/14 06:00
PHST- 2017/11/29 00:00 [received]
PHST- 2018/01/31 00:00 [revised]
PHST- 2018/02/02 00:00 [accepted]
PHST- 2018/02/14 06:00 [pubmed]
PHST- 2018/02/14 06:00 [medline]
PHST- 2018/02/14 06:00 [entrez]
AID - CIRCRESAHA.117.312472 [pii]
AID - 10.1161/CIRCRESAHA.117.312472 [doi]
PST - ppublish
SO  - Circ Res. 2018 Mar 16;122(6):855-863. doi: 10.1161/CIRCRESAHA.117.312472. Epub
      2018 Feb 5.