title: Lack of angiopoietin-like-2 expression limits the metabolic stress induced by a high-fat diet and maintains endothelial function in mice.
abstract: 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.
  
  
  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.
authors.affiliation: Departments of Pharmacology and Surgery, Faculty of Medicine, Université de Montréal, 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.).
authors.forename: Carol
authors.initials: C
authors.lastname: Yu
authors.affiliation: 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.).
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Luo
authors.affiliation: Departments of Pharmacology and Surgery, Faculty of Medicine, Université de Montréal, 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.).
authors.forename: Nada
authors.initials: N
authors.lastname: Farhat
authors.affiliation: 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.).
authors.forename: Caroline
authors.initials: C
authors.lastname: Daneault
authors.affiliation: 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.).
authors.forename: Natacha
authors.initials: N
authors.lastname: Duquette
authors.affiliation: 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.).
authors.forename: Cécile
authors.initials: C
authors.lastname: Martel
authors.affiliation: Departments of Social and Preventive Medicine, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada (J.L.).
authors.forename: Jean
authors.initials: J
authors.lastname: Lambert
authors.affiliation: 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.).
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thorin-Trescases
authors.affiliation: Department of Nutrition, Faculty of Medicine, Université de Montréal, 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.).
authors.forename: Christine Des
authors.initials: CD
authors.lastname: Rosiers
authors.affiliation: Departments of Pharmacology and Surgery, Faculty of Medicine, Université de Montréal, 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.).
authors.forename: Eric
authors.initials: E
authors.lastname: Thorin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000111:Acetylcysteine / Q000494:pharmacology; D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011464:Epoprostenol / Q000378:metabolism; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics*
chemical_list: D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D011464:Epoprostenol; D000109:Acetylcholine; D000111:Acetylcysteine
keywords: adipokines; endothelium‐derived relaxing factors; inflammation; isolated arteries