PMID- 19407006
OWN - NLM
STAT- MEDLINE
DCOM- 20091002
LR  - 20220330
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 50
IP  - 10
DP  - 2009 Oct
TI  - Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid 
      mediators.
PG  - 4743-52
LID - 10.1167/iovs.08-2462 [doi]
AB  - PURPOSE: Resolvins and lipoxins are lipid mediators generated from essential 
      polyunsaturated fatty acids that are the first dual anti-inflammatory and 
      pro-resolving signals identified in the resolution phase of inflammation. Here 
      the authors investigated the potential of aspirin-triggered lipoxin (LX) A4 
      analog (ATLa), resolving (Rv) D1, and RvE1, in regulating angiogenesis in a 
      murine model. METHODS: ATLa and RvE1 receptor expression was tested in different 
      corneal cell populations by RT-PCR. Corneal neovascularization (CNV) was induced 
      by suture or micropellet (IL-1 beta, VEGF-A) placement. Mice were then treated 
      with ATLa, RvD1, RvE1, or vehicle, subconjunctivally at 48-hour intervals. 
      Infiltration of neutrophils and macrophages was quantified after 
      immunofluorescence staining. The mRNA expression levels of inflammatory 
      cytokines, VEGFs, and VEGFRs were analyzed by real-time PCR. CNV was evaluated 
      intravitally and morphometrically. RESULTS: The receptors for LXA4, ALX/Fpr-rs-2 
      and for RvE1, ChemR23 were each expressed by epithelium, stromal keratocytes, and 
      infiltrated CD11b(+) cells in corneas. Compared to the vehicle-treated eye, 
      ATLa-, RvD1-, and RvE1-treated eyes had reduced numbers of infiltrating 
      neutrophils and macrophages and reduced mRNA expression levels of TNF-alpha, IL-1 
      alpha, IL-1 beta, VEGF-A, VEGF-C, and VEGFR2. Animals treated with these 
      mediators had significantly suppressed suture-induced or IL-1 beta-induced 
      hemangiogenesis (HA) but not lymphangiogenesis. Interestingly, only the 
      application of ATLa significantly suppressed VEGF-A-induced HA. CONCLUSIONS: 
      ATLa, RvE1, and RvD1 all reduce inflammatory corneal HA by early regulation of 
      resolution mechanisms in innate immune responses. In addition, ATLa directly 
      inhibits VEGF-A-mediated angiogenesis and is the most potent inhibitor of NV 
      among this new genus of dual anti-inflammatory and pro-resolving lipid mediators.
FAU - Jin, Yiping
AU  - Jin Y
AD  - Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical 
      School, 20 Staniford Street, Boston, MA 02114, USA.
FAU - Arita, Makoto
AU  - Arita M
FAU - Zhang, Qiang
AU  - Zhang Q
FAU - Saban, Daniel R
AU  - Saban DR
FAU - Chauhan, Sunil K
AU  - Chauhan SK
FAU - Chiang, Nan
AU  - Chiang N
FAU - Serhan, Charles N
AU  - Serhan CN
FAU - Dana, Reza
AU  - Dana R
LA  - eng
GR  - P20 RR020753/RR/NCRR NIH HHS/United States
GR  - R01-EY 12963/EY/NEI NIH HHS/United States
GR  - GM38675/GM/NIGMS NIH HHS/United States
GR  - P20 RR20753/RR/NCRR NIH HHS/United States
GR  - P50 DE0169191/DE/NIDCR NIH HHS/United States
GR  - R01 EY012963/EY/NEI NIH HHS/United States
GR  - R01 EY012963-09/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090430
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (16-(4-fluoro)phenoxylipoxin A4 methyl ester)
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Cytokines)
RN  - 0 (Fpr1 protein, mouse)
RN  - 0 (Lipoxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factor C)
RN  - 0 (resolvin D1)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - 0 (vascular endothelial growth factor C, mouse)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
RN  - GND3JH08JA (5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Corneal Neovascularization/*drug therapy/genetics/immunology
MH  - Cytokines/genetics
MH  - *Disease Models, Animal
MH  - Docosahexaenoic Acids/*pharmacology
MH  - Down-Regulation
MH  - Eicosapentaenoic Acid/*analogs & derivatives/pharmacology
MH  - Fluorescent Antibody Technique, Indirect
MH  - Lipoxins/*pharmacology
MH  - Macrophages/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neutrophils/physiology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Formyl Peptide/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor A/genetics
MH  - Vascular Endothelial Growth Factor C/genetics
MH  - Vascular Endothelial Growth Factor Receptor-2/genetics
PMC - PMC2763387
MID - NIHMS126195
EDAT- 2009/05/02 09:00
MHDA- 2009/10/03 06:00
PMCR- 2010/10/01
CRDT- 2009/05/02 09:00
PHST- 2009/05/02 09:00 [entrez]
PHST- 2009/05/02 09:00 [pubmed]
PHST- 2009/10/03 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - iovs.08-2462 [pii]
AID - 10.1167/iovs.08-2462 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4743-52. doi: 10.1167/iovs.08-2462. 
      Epub 2009 Apr 30.