Macrophage activation is responsible for loss of anticontractile function in inflamed perivascular fat
| Autor: | Daniel M. Livingstone, Rehima Aslam, Matthew C. Little, Rayaz A. Malik, Claudia Agabiti-Rosei, Sarah B Withers, Anthony M. Heagerty |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Aldosterone metabolism Perivascular fat Adipose tissue Inflammation Biology In Vitro Techniques Microcirculation Mice Internal medicine medicine Macrophage Animals Vasoconstrictor Agents Rats Wistar Aldosterone Mineralocorticoid Receptor Antagonists Mice Knockout CD11b Antigen Electrical impedance myography Dose-Response Relationship Drug Macrophages Myography Free Radical Scavengers Macrophage Activation Cell Hypoxia Mesenteric Arteries Rats Oxidative Stress Endocrinology Adipose Tissue Vasoconstriction Intercellular Signaling Peptides and Proteins medicine.symptom Inflammation Mediators Cardiology and Cardiovascular Medicine Function (biology) Heparin-binding EGF-like Growth Factor |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 31(4) |
| ISSN: | 1524-4636 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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