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.
Highlights
APN, a pleiotropic adipokine which exerts profound anti-inflammatory and atherogenic effects in vascular cells, is potential therapeutic target to prevent vascular inflammation and damage[11,12]
We investigated the therapeutic role of increasing plasma APN levels on AngII-induced advanced Abdominal aortic aneurysm (AAA) development in a well-established preclinical model
We have previously established that APN expresson to increase plasma APN levels effectively inhibits AngII-mediated vascular inflammation and accelerated atherosclerosis[11]
Summary
APN, a pleiotropic adipokine which exerts profound anti-inflammatory and atherogenic effects in vascular cells, is potential therapeutic target to prevent vascular inflammation and damage[11,12]. We have established the protective role of APN against AngII-induced vascular inflammation and accelerated atherosclerosis in the hyperlipidemic LDLR−/− model[11]. A recent report showed that complete APN knockout in apolipoprotein E-deficient mice increased AngII-induced inflammation and early AAA8. We investigated the therapeutic potential of increasing plasma APN levels to prevent advanced AAA in the well-established AngII-induced hyperlipidemic LDLR−/− model in which AngII suppressed endogenous APN expression. We addressed the hypothesis that APN expression increasing plasma APN levels inhibits aortic, perivascular and visceral adipose inflammation, medial degeneration and elastin degradation in the aneurysmal wall to prevent advanced AAA development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
