title: Macrophage activation is responsible for loss of anticontractile function in inflamed perivascular fat.
abstract: OBJECTIVE
  The aim of this study was to determine whether macrophages dispersed throughout perivascular fat are crucial to the loss of anticontractile function when healthy adipose tissue becomes inflamed and to gain an understanding of the mechanisms involved.
  
  
  RESULTS
  Pharmacological studies on in vitro small arterial segments from a mouse model of inducible macrophage ablation and on wild-type animals were carried out with and without perivascular fat using 2 physiological stimuli of inflammation: aldosterone and hypoxia. Both inflammatory insults caused a similar loss of anticontractile capacity of perivascular fat and increased macrophage activation. Aldosterone receptor antagonism and free radical scavengers were able to restore this capacity and reduce macrophage activation. However, in a mouse deficient of macrophages CD11b-diptheria toxin receptor (CD11b-DTR), there was no increase in contractility of arteries following aldosterone incubation or hypoxia.
  
  
  CONCLUSIONS
  The presence and activation of macrophages in adipose tissue is the key modulator of the increase in contractility in arteries with perivascular fat following induction of inflammation. Despite multiple factors that may be involved in bringing about the vascular consequences of obesity, the ability of eplerenone to ameliorate the inflammatory effects of both aldosterone and hypoxia may be of potential therapeutic interest.
authors.affiliation: Cardiovascular Research Group, Faculty of Medical & Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Withers
authors.forename: Claudia
authors.initials: C
authors.lastname: Agabiti-Rosei
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Livingstone
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Little
authors.forename: Rehima
authors.initials: R
authors.lastname: Aslam
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D066257:Heparin-binding EGF-like Growth Factor; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009213:Myography; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D039481:CD11b Antigen; D016166:Free Radical Scavengers; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D000451:Mineralocorticoid Receptor Antagonists; D014662:Vasoconstrictor Agents; D000450:Aldosterone