Macrophage activation is responsible for loss of anticontractile function in inflamed perivascular fat

Sarah B. Withers, Claudia Agabiti-Rosei, Daniel M. Livingstone, Matthew C. Little, Rehima Aslam, Rayaz Malik, Anthony M. Heagerty

Research output: Contribution to journalArticle

69 Citations (Scopus)

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. Methods and 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. Conclusion- 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.

Original languageEnglish
Pages (from-to)908-913
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number4
DOIs
Publication statusPublished - Apr 2011
Externally publishedYes

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Keywords

  • hypoxia
  • inflammation
  • microcirculation
  • obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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