title: Elevated Adiponectin Levels Suppress Perivascular and Aortic Inflammation and Prevent AngII-induced Advanced Abdominal Aortic Aneurysms.
abstract: 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.
authors.affiliation: Division of Drug research, Department of Medical and Health Sciences, Faculty of Health Science, Linköping University, Linköping, Sweden.
authors.forename: Dick
authors.initials: D
authors.lastname: Wågsäter
authors.affiliation: Division of Drug research, Department of Medical and Health Sciences, Faculty of Health Science, Linköping University, Linköping, Sweden.
authors.forename: Emina
authors.initials: E
authors.lastname: Vorkapic
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, USA.
authors.forename: Caroline M W
authors.initials: CM
authors.lastname: van Stijn
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA.
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.affiliation: Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, USA.|Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA.
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Tangirala