Abstract 12448: AMPKα1 Knockout Mice Have Dysfunctional Perivascular Adipose Tissue (PVAT) and Impaired Vascular Function
Introduction: Perivascular adipose tissue (PVAT) surrounds blood vessels and releases many mediators which regulate vascular tone. AMP-activated protein kinase (AMPK) is a critical regulator of cellular metabolism and although expressed throughout the vessel wall, its function in PVAT is unknown. Although aortic PVAT from mice with global AMPKα1 knockout releases significantly less adiponectin and does not augment vasodilator responses in isolated vessels, these mice remain normotensive.
Hypothesis: Mice with global AMPKα1 deficiency will have inflamed PVAT and that high fat feeding will increase PVAT inflammation further and raise blood pressure.
Methods: Unfixed samples of wild-type (WT) and KO aortic PVAT (n>3 for each) were incubated with dihydroethidium (DHE) or 4,5 diaminofluorescein diacetate (DAF-2DA) to detect superoxide and NO respectively. Images were captured using a fluorescence microscope. Nitrotyrosine expression and macrophages in the PVAT were examined using immunohistochemistry and FACS respectively. Matched KO and WT littermates were fed either chow diet or hfd (21% lard, 0.15% chol.) for up to 12 weeks and BP measured by tail-cuff plethysmography every 4 weeks. Measurement of vascular function in aortic rings was via wire myography and adiponectin release was measured using ELISA assay.
Results: In aortic PVAT, superoxide and NO production was unchanged in KO mice but nitrotyrosine expression and macrophage content was significantly higher. In WT mice, 12 weeks of hfd attenuated vasodilator responses of aortic rings containing PVAT (n=6; p<0.05) and reduced adiponectin production by PVAT. In KO rings containing PVAT the vasodilator response was already suppressed and hfd did not lower it further or alter production of adiponectin. High fat diet increased PVAT macrophage content of both WT and KO but did not alter mean arterial BP after 8 weeks in either strain.
Conclusions: AMPK in aortic PVAT regulates production of adiponectin and suppresses inflammation. Mice lacking AMPKα1 lose the beneficial effects of PVAT on vascular relaxation and while fat feeding increases inflammation of the PVAT, BP did not rise, perhaps through compensation effects in smooth muscle or endothelial function.
Author Disclosures: T.A. Almabrouk: None. A. Riddell: None. A.B. Ugusman: None. I.P. Salt: None. S. Kennedy: None.
- © 2016 by American Heart Association, Inc.