PMID- 29559676
OWN - NLM
STAT- MEDLINE
DCOM- 20191104
LR  - 20221207
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Mar 20
TI  - Obesity-induced Endothelial Dysfunction is Prevented by Neutrophil Extracellular 
      Trap Inhibition.
PG  - 4881
LID - 10.1038/s41598-018-23256-y [doi]
LID - 4881
AB  - Endothelial dysfunction precedes atherosclerosis and may constitute a critical 
      link between obesity-related inflammation and cardiovascular disease. Neutrophil 
      extracellular traps (NETs) have been shown to promote vascular damage in murine 
      models of autoimmune disease and atherosclerosis. The impact of NETs towards 
      endothelial dysfunction associated with obesity is unknown. Using a diet-induced 
      obesity (DIO) mouse model, this study investigated whether the inhibition or 
      degradation of NETs could reduce the endothelial dysfunction observed in DIO 
      mice. Following induction of DIO, there were elevated plasma concentrations of 
      monocyte chemoattractant protein-1 (MCP-1) and impairment of mesenteric 
      arteriolar vasorelaxation in response to acetylcholine as measured by pressure 
      myography. A marker of NET formation, cathelicidin-related antimicrobial peptide 
      (CRAMP), was markedly increased in mesenteric arterial walls of DIO mice compared 
      to mice on standard chow. Prevention of NET formation with Cl-amidine or 
      dissolution of NETs with DNase restored endothelium-dependent vasodilation to the 
      mesenteric arteries of DIO mice. These findings suggest an instrumental role for 
      NETs in obesity-induced endothelial dysfunction.
FAU - Wang, Hui
AU  - Wang H
AD  - University of Michigan, Department of Internal Medicine, Cardiovascular Research 
      Center, Ann Arbor, Michigan, USA.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Cardiology, the Fourth Affiliated Hospital of China Medical 
      University, Shenyang, China.
FAU - Venugopal, Jessica
AU  - Venugopal J
AD  - University of Michigan, Department of Internal Medicine, Cardiovascular Research 
      Center, Ann Arbor, Michigan, USA.
FAU - Wang, Jintao
AU  - Wang J
AD  - University of Michigan, Department of Internal Medicine, Cardiovascular Research 
      Center, Ann Arbor, Michigan, USA.
FAU - Kleiman, Kyle
AU  - Kleiman K
AD  - University of Michigan, Department of Internal Medicine, Cardiovascular Research 
      Center, Ann Arbor, Michigan, USA.
FAU - Guo, Chiao
AU  - Guo C
AD  - University of Michigan, Department of Internal Medicine, Cardiovascular Research 
      Center, Ann Arbor, Michigan, USA.
FAU - Eitzman, Daniel T
AU  - Eitzman DT
AD  - University of Michigan, Department of Internal Medicine, Cardiovascular Research 
      Center, Ann Arbor, Michigan, USA. deitzman@umich.edu.
LA  - eng
GR  - T32 HL007853/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180320
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cathelicidins)
SB  - IM
MH  - Animals
MH  - Antimicrobial Cationic Peptides/analysis/blood
MH  - Cardiovascular Diseases/physiopathology
MH  - Chemokine CCL2/analysis/blood
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/*metabolism
MH  - Extracellular Traps/*metabolism/physiology
MH  - Inflammation/metabolism
MH  - Male
MH  - Mesenteric Arteries/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Obesity/physiopathology
MH  - Vascular Diseases/physiopathology
MH  - Vasodilation
MH  - Cathelicidins
PMC - PMC5861102
COIS- The authors declare no competing interests.
EDAT- 2018/03/22 06:00
MHDA- 2019/11/05 06:00
PMCR- 2018/03/20
CRDT- 2018/03/22 06:00
PHST- 2017/10/06 00:00 [received]
PHST- 2018/03/08 00:00 [accepted]
PHST- 2018/03/22 06:00 [entrez]
PHST- 2018/03/22 06:00 [pubmed]
PHST- 2019/11/05 06:00 [medline]
PHST- 2018/03/20 00:00 [pmc-release]
AID - 10.1038/s41598-018-23256-y [pii]
AID - 23256 [pii]
AID - 10.1038/s41598-018-23256-y [doi]
PST - epublish
SO  - Sci Rep. 2018 Mar 20;8(1):4881. doi: 10.1038/s41598-018-23256-y.