PMID- 25527773
OWN - NLM
STAT- MEDLINE
DCOM- 20150501
LR  - 20211203
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 308
IP  - 5
DP  - 2015 Mar 1
TI  - Knockdown of angiopoietin like-2 protects against angiotensin II-induced cerebral 
      endothelial dysfunction in mice.
PG  - H386-97
LID - 10.1152/ajpheart.00278.2014 [doi]
AB  - Angiopoietin like-2 (angptl2) is a circulating pro-inflammatory and pro-oxidative 
      protein, but its role in regulating cerebral endothelial function remains 
      unknown. We hypothesized that in mice knockdown (KD) of angptl2, cerebral 
      endothelial function would be protected against ANG II-induced damage. 
      Subcutaneous infusion of ANG II (200 ng.kg(-1).min(-1), n = 15) or saline (n = 
      15) was performed in 20-wk-old angptl2 KD mice and wild-type (WT) littermates for 
      14 days. In saline-treated KD and WT mice, the amplitude and the sensitivity of 
      ACh-induced dilations of isolated cerebral arteries were similar. However, while 
      endothelial nitric oxide (NO) synthase (eNOS)-derived O2 (-)/H2O2 contributed to 
      dilation in WT mice, eNOS-derived NO (P < 0.05) was involved in KD mice. ANG II 
      induced cerebral endothelial dysfunction only in WT mice (P < 0.05), which was 
      reversed (P < 0.05) by either N-acetyl-l-cysteine, apocynin, gp91ds-tat, or 
      indomethacin, suggesting the contribution of reactive oxygen species from Nox2 
      and Cox-derived contractile factors. In KD mice treated with ANG II, endothelial 
      function was preserved, likely via Nox-derived H2O2, sensitive to apocynin and 
      PEG-catalase (P < 0.05), but not to gp91ds-tat. In the aorta, relaxation 
      similarly and essentially depended on NO; endothelial function was maintained 
      after ANG II infusion in all groups, but apocynin significantly reduced aortic 
      relaxation in KD mice (P < 0.05). Protein expression levels of Nox1/2 in cerebral 
      arteries were similar among all groups, but that of Nox4 was greater (P < 0.05) 
      in saline-treated KD mice. In conclusion, knockdown of angptl2 may be protective 
      against ANG II-induced cerebral endothelial dysfunction; it favors the production 
      of NO, likely increasing endothelial cell resistance to stress, and permits the 
      expression of an alternative vasodilatory Nox pathway.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - Yu, Carol
AU  - Yu C
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada; Department 
      of Pharmacology, Faculty of Medicine, Universite de Montreal, Montreal, Quebec, 
      Canada; and.
FAU - Luo, Xiaoyan
AU  - Luo X
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada;
FAU - Duquette, Natacha
AU  - Duquette N
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada;
FAU - Thorin-Trescases, Nathalie
AU  - Thorin-Trescases N
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada;
FAU - Thorin, Eric
AU  - Thorin E
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada; Department 
      of Surgery, Faculty of Medicine, Universite de Montreal, Montreal, Quebec, Canada 
      eric.thorin@umontreal.ca.
LA  - eng
GR  - MOP 14496/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141219
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Acetophenones)
RN  - 0 (Angiopoietin-Like Protein 2)
RN  - 0 (Angiopoietin-like Proteins)
RN  - 0 (Angiopoietins)
RN  - 0 (Angptl2 protein, mouse)
RN  - 0 (Glycoproteins)
RN  - 0 (gp91ds-tat protein, chimeric)
RN  - 11128-99-7 (Angiotensin II)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - B6J7B9UDTR (acetovanillone)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - N9YNS0M02X (Acetylcholine)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Acetophenones/pharmacology
MH  - Acetylcholine/pharmacology
MH  - Angiopoietin-Like Protein 2
MH  - Angiopoietin-like Proteins
MH  - Angiopoietins/genetics/*metabolism
MH  - Angiotensin II/*pharmacology
MH  - Animals
MH  - Cerebral Arteries/cytology/*metabolism/physiology
MH  - Endothelium, Vascular/drug effects/*metabolism/physiology
MH  - Gene Deletion
MH  - Glycoproteins/pharmacology
MH  - Hydrogen Peroxide/metabolism
MH  - Indomethacin/pharmacology
MH  - Mice
MH  - NADPH Oxidases/metabolism
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/antagonists & inhibitors/metabolism
MH  - *Vasoconstriction
OTO - NOTNLM
OT  - NADPH oxidases
OT  - angiopoietin like-2
OT  - cerebral arteries
OT  - endothelium
OT  - nitric oxide
EDAT- 2014/12/21 06:00
MHDA- 2015/05/02 06:00
CRDT- 2014/12/21 06:00
PHST- 2014/12/21 06:00 [entrez]
PHST- 2014/12/21 06:00 [pubmed]
PHST- 2015/05/02 06:00 [medline]
AID - ajpheart.00278.2014 [pii]
AID - 10.1152/ajpheart.00278.2014 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2015 Mar 1;308(5):H386-97. doi: 
      10.1152/ajpheart.00278.2014. Epub 2014 Dec 19.