title: Superoxide signaling in perivascular adipose tissue promotes age-related artery stiffness.
abstract: We tested the hypothesis that superoxide signaling within aortic perivascular adipose tissue (PVAT) contributes to large elastic artery stiffening in old mice. Young (4-6 months), old (26-28 months), and old treated with 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide scavenger (1 mm in drinking water for 3 weeks), male C57BL6/N mice were studied. Compared with young, old had greater large artery stiffness assessed by aortic pulse wave velocity (aPWV, 436 ± 9 vs. 344 ± 5 cm s(-1)) and intrinsic mechanical testing (3821 ± 427 vs. 1925 ± 271 kPa) (both P < 0.05). TEMPOL treatment in old reversed both measures of arterial stiffness. Aortic PVAT superoxide production was greater in old (P < 0.05 vs. Y), which was normalized with TEMPOL. Compared with young, old controls had greater pro-inflammatory proteins in PVAT-conditioned media (P < 0.05). Young recipient mice transplanted with PVAT from old compared with young donors for 8 weeks had greater aPWV (409 ± 7 vs. 342 ± 8 cm s(-1)) and intrinsic mechanical properties (3197 ± 647 vs. 1889 ± 520 kPa) (both P < 0.05), which was abolished with TEMPOL supplementation in old donors. Tissue-cultured aortic segments from old in the presence of PVAT had greater mechanical stiffening compared with old cultured in the absence of PVAT and old with PVAT and TEMPOL (both, P < 0.05). In addition, PVAT-derived superoxide was associated with arterial wall hypertrophy and greater adventitial collagen I expression with aging that was attenuated by TEMPOL. Aging or TEMPOL treatment did not affect blood pressure. Our findings provide evidence for greater age-related superoxide production and pro-inflammatory proteins in PVAT, and directly link superoxide signaling in PVAT to large elastic artery stiffness.
authors.affiliation: Department of Integrative Physiology, University of Colorado, Boulder, CO, USA; Kinesiology and Health Promotion, Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Fleenor
authors.forename: Jason S
authors.initials: JS
authors.lastname: Eng
authors.forename: Amy L
authors.initials: AL
authors.lastname: Sindler
authors.forename: Bryant T
authors.initials: BT
authors.lastname: Pham
authors.forename: Jackson D
authors.initials: JD
authors.lastname: Kloor
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D059289:Vascular Stiffness / Q000502:physiology*
chemical_list: D013481:Superoxides
keywords: TEMPOL; fat; oxidative stress; peri-aortic