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Elevated Adiponectin Levels Suppress Perivascular and Aortic Inflammation and Prevent AngII-induced Advanced Abdominal Aortic Aneurysms
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
University of Calif Los Angeles, CA 90095 USA.
University of Calif Los Angeles, CA 90095 USA.
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 31414Article in journal (Refereed) Published
Abstract [en]

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by aortic dilation and rupture leading to sudden death. Currently, no non-surgical treatments are available and novel therapeutic targets are needed to prevent AAA. We investigated whether increasing plasma levels of adiponectin (APN), a pleiotropic adipokine, provides therapeutic benefit to prevent AngII-induced advanced AAA in a well-established preclinical model. In the AngII-infused hyperlipidemic low-density lipoprotein receptor-deficient mouse (LDLR-/-) model, we induced plasma APN levels using a recombinant adenovirus expressing mouse APN (AdAPN) and as control, adenovirus expressing green florescent protein (AdGFP). APN expression produced sustained and significant elevation of total and high-molecular weight APN levels and enhanced APN localization in the artery wall. AngII infusion for 8 weeks induced advanced AAA development in AdGFP mice. Remarkably, APN inhibited the AAA development in AdAPN mice by suppressing aortic inflammatory cell infiltration, medial degeneration and elastin fragmentation. APN inhibited the angiotensin type-1 receptor (AT1R), inflammatory cytokine and mast cell protease expression, and induced lysyl oxidase (LOX) in the aortic wall, improved systemic cytokine profile and attenuated adipose inflammation. These studies strongly support APN therapeutic actions through multiple mechanisms inhibiting AngII-induced AAA and increasing plasma APN levels as a strategy to prevent advanced AAA.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2016. Vol. 6, 31414
National Category
Pharmacology and Toxicology
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URN: urn:nbn:se:liu:diva-132053DOI: 10.1038/srep31414ISI: 000383914700001PubMedID: 27659201OAI: oai:DiVA.org:liu-132053DiVA: diva2:1038467
Note

Funding Agencies|National Institutes of Health grant [HL086566]; Carl and Roberta Deutsch Family Foundation; Swedish Research Council [K2013-99X-22231-01-5]; Stiftelseforvaltningen, Ssk Siv Olssons forskningsstiftelse [92100]

Available from: 2016-10-18 Created: 2016-10-17 Last updated: 2016-11-11

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Wågsäter, DickVorkapic, Emina
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