PMID- 25128474
OWN - NLM
STAT- MEDLINE
DCOM- 20150928
LR  - 20211203
IS  - 2047-9980 (Electronic)
IS  - 2047-9980 (Linking)
VI  - 3
IP  - 4
DP  - 2014 Aug 15
TI  - Lack of angiopoietin-like-2 expression limits the metabolic stress induced by a 
      high-fat diet and maintains endothelial function in mice.
LID - 10.1161/JAHA.114.001024 [doi]
LID - e001024
AB  - BACKGROUND: Angiopoietin-like-2 (angptl2) is produced by several cell types 
      including endothelial cells, adipocytes and macrophages, and contributes to the 
      inflammatory process in cardiovascular diseases. We hypothesized that angptl2 
      impairs endothelial function, and that lowering angptl2 levels protects the 
      endothelium against high-fat diet (HFD)-induced fat accumulation and 
      hypercholesterolemia. METHODS AND RESULTS: Acute recombinant angptl2 reduced 
      (P<0.05) acetylcholine-mediated vasodilation of isolated wild-type (WT) mouse 
      femoral artery, an effect reversed (P<0.05) by the antioxidant N-acetylcysteine. 
      Accordingly, in angptl2 knockdown (KD) mice, ACh-mediated endothelium-dependent 
      vasodilation was greater (P<0.05) than in WT mice. In arteries from KD mice, 
      prostacyclin contributed to the overall dilation unlike in WT mice. After a 
      3-month HFD, overall vasodilation was not altered, but dissecting out the 
      endothelial intrinsic pathways revealed that NO production was reduced in 
      arteries isolated from HFD-fed WT mice (P<0.05), while NO release was maintained 
      in KD mice. Similarly, endothelium-derived hyperpolarizing factor (EDHF) was 
      preserved in mesenteric arteries from HFD-fed KD mice but not in those from WT 
      mice. Finally, the HFD increased (P<0.05) total cholesterol-to-high-density 
      lipoprotein ratios, low-density lipoprotein-to-high-density lipoprotein ratios, 
      and leptin levels in WT mice only, while glycemia remained similar in the 2 
      strains. KD mice displayed less triglyceride accumulation in the liver (P<0.05 
      versus WT), and adipocyte diameters in mesenteric and epididymal white adipose 
      tissues were smaller (P<0.05) in KD than in WT fed an HFD, while inflammatory 
      gene expression increased (P<0.05) in the fat of WT mice only. CONCLUSIONS: Lack 
      of angptl2 expression limits the metabolic stress induced by an HFD and maintains 
      endothelial function in mice.
CI  - (c) 2014 The Authors. Published on behalf of the American Heart Association, Inc., 
      by Wiley Blackwell.
FAU - Yu, Carol
AU  - Yu C
AD  - Departments of Pharmacology and Surgery, Faculty of Medicine, Universite de 
      Montreal, Montreal, Quebec, Canada (C.Y., N.F., T.) Montreal Heart Institute, 
      Research Center, Montreal, Quebec, Canada (C.Y., X.L., N.F., C.D., N.D., M., 
      N.T.T., C.D.R., T.).
FAU - Luo, Xiaoyan
AU  - Luo X
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada (C.Y., X.L., 
      N.F., C.D., N.D., M., N.T.T., C.D.R., T.).
FAU - Farhat, Nada
AU  - Farhat N
AD  - Departments of Pharmacology and Surgery, Faculty of Medicine, Universite de 
      Montreal, Montreal, Quebec, Canada (C.Y., N.F., T.) Montreal Heart Institute, 
      Research Center, Montreal, Quebec, Canada (C.Y., X.L., N.F., C.D., N.D., M., 
      N.T.T., C.D.R., T.).
FAU - Daneault, Caroline
AU  - Daneault C
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada (C.Y., X.L., 
      N.F., C.D., N.D., M., N.T.T., C.D.R., T.).
FAU - Duquette, Natacha
AU  - Duquette N
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada (C.Y., X.L., 
      N.F., C.D., N.D., M., N.T.T., C.D.R., T.).
FAU - Martel, Cecile
AU  - Martel C
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada (C.Y., X.L., 
      N.F., C.D., N.D., M., N.T.T., C.D.R., T.).
FAU - Lambert, Jean
AU  - Lambert J
AD  - Departments of Social and Preventive Medicine, Faculty of Medicine, Universite de 
      Montreal, Montreal, Quebec, Canada (J.L.).
FAU - Thorin-Trescases, Nathalie
AU  - Thorin-Trescases N
AD  - Montreal Heart Institute, Research Center, Montreal, Quebec, Canada (C.Y., X.L., 
      N.F., C.D., N.D., M., N.T.T., C.D.R., T.).
FAU - Rosiers, Christine Des
AU  - Rosiers CD
AD  - Department of Nutrition, Faculty of Medicine, Universite de Montreal, Montreal, 
      Quebec, Canada (C.D.R.) Montreal Heart Institute, Research Center, Montreal, 
      Quebec, Canada (C.Y., X.L., N.F., C.D., N.D., M., N.T.T., C.D.R., T.).
FAU - Thorin, Eric
AU  - Thorin E
AD  - Departments of Pharmacology and Surgery, Faculty of Medicine, Universite de 
      Montreal, Montreal, Quebec, Canada (C.Y., N.F., T.) Montreal Heart Institute, 
      Research Center, Montreal, Quebec, Canada (C.Y., X.L., N.F., C.D., N.D., M., 
      N.T.T., C.D.R., T.).
LA  - eng
GR  - MOP 133649/Canadian Institutes of Health Research/Canada
GR  - MOP 14496/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140815
PL  - England
TA  - J Am Heart Assoc
JT  - Journal of the American Heart Association
JID - 101580524
RN  - 0 (Angiopoietin-Like Protein 2)
RN  - 0 (Angiopoietin-like Proteins)
RN  - 0 (Angiopoietins)
RN  - 0 (Angptl2 protein, mouse)
RN  - 0 (Free Radical Scavengers)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - N9YNS0M02X (Acetylcholine)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Acetylcysteine/pharmacology
MH  - Angiopoietin-Like Protein 2
MH  - Angiopoietin-like Proteins
MH  - Angiopoietins/*genetics/metabolism
MH  - Animals
MH  - *Diet, High-Fat
MH  - Endothelium, Vascular/drug effects/*metabolism/physiopathology
MH  - Epoprostenol/metabolism
MH  - Femoral Artery/drug effects/*metabolism/physiopathology
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Knockdown Techniques
MH  - Mice
MH  - Nitric Oxide/metabolism
MH  - Oxidative Stress/drug effects/*genetics
MH  - Vasodilation/drug effects/*genetics
PMC - PMC4310393
OTO - NOTNLM
OT  - adipokines
OT  - endothelium-derived relaxing factors
OT  - inflammation
OT  - isolated arteries
EDAT- 2014/08/17 06:00
MHDA- 2015/09/29 06:00
PMCR- 2014/08/01
CRDT- 2014/08/17 06:00
PHST- 2014/08/17 06:00 [entrez]
PHST- 2014/08/17 06:00 [pubmed]
PHST- 2015/09/29 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - jah3618 [pii]
AID - 10.1161/JAHA.114.001024 [doi]
PST - epublish
SO  - J Am Heart Assoc. 2014 Aug 15;3(4):e001024. doi: 10.1161/JAHA.114.001024.