title: Chemerin connects fat to arterial contraction.
abstract: OBJECTIVE
  Obesity and hypertension are comorbid in epidemic proportion, yet their biological connection is largely a mystery. The peptide chemerin is a candidate for connecting fat deposits around the blood vessel (perivascular adipose tissue) to arterial contraction. We presently tested the hypothesis that chemerin is expressed in perivascular adipose tissue and is vasoactive, supporting the existence of a chemerin axis in the vasculature.
  
  
  RESULTS
  Real-time polymerase chain reaction, immunohistochemistry, and Western analyses supported the synthesis and expression of chemerin in perivascular adipose tissue, whereas the primary chemerin receptor ChemR23 was expressed both in the tunica media and endothelial layer. The ChemR23 agonist chemerin-9 caused receptor, concentration-dependent contraction in the isolated rat thoracic aorta, superior mesenteric artery, and mesenteric resistance artery, and contraction was significantly amplified (more than 100%) when nitric oxide synthase was inhibited and the endothelial cell mechanically removed or tone was placed on the arteries. The novel ChemR23 antagonist CCX832 inhibited phenylephrine-induced and prostaglandin F2α-induced contraction (+perivascular adipose tissue), suggesting that endogenous chemerin contributes to contraction. Arteries from animals with dysfunctional endothelium (obese or hypertensive) demonstrated a pronounced contraction to chemerin-9. Finally, mesenteric arteries from obese humans demonstrate amplified contraction to chemerin-9.
  
  
  CONCLUSIONS
  These data support a new role for chemerin as an endogenous vasoconstrictor that operates through a receptor typically attributed to function only in immune cells.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA. wattss@msu.edu
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Watts
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dorrance
authors.forename: Mark E
authors.initials: ME
authors.lastname: Penfold
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Rourke
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sinal
authors.forename: Bridget
authors.initials: B
authors.lastname: Seitz
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sullivan
authors.forename: Trevor T
authors.initials: TT
authors.lastname: Charvat
authors.forename: Janice M
authors.initials: JM
authors.lastname: Thompson
authors.forename: Robert
authors.initials: R
authors.lastname: Burnett
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Fink
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D018925:Chemokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007120:Immunochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009765:Obesity / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D054392:Adipokines; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; C560738:Rarres2 protein, rat; D000804:Angiotensin II; D010656:Phenylephrine
keywords: ChemR23; PVAT; adipose tissue; chemerin; vasoconstriction
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