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.
Digital Object Identifier (DOI)
Fleenor, Bradley S.; Eng, Jason S.; Sindler, Amy L.; Pham, Bryant T.; Kloor, Jackson D.; and Seals, Douglas R., "Superoxide Signaling in Perivascular Adipose Tissue Promotes Age-Related Artery Stiffness" (2014). Graduate Center for Nutritional Sciences Faculty Publications. 7.
Data S1 Experimental procedures.
acel12196-sup-0002-TableS1-S2-FigS1-S4.pdf (22831 kB)
Table S1 Arterial morphology and blood pressure in young, old and old TEMPOL-treated mice. Table S2 Arterial morphology and blood pressure in young recipient mice after transplanted with PVAT from young, old or old TEMPOLtreated donors for 8 weeks. Fig. S1 Adventitial collagen I expression in young, old and old TEMPOL-treated mice. Fig. S2 Superoxide production in adipocytes isolated from PVAT of young and old mice. Fig. S3 Cytokine secretion profile of cultured PVAT from young and old mice. Fig. S4 Adventitial collagen I expression in young recipient mice transplanted with PVAT from young, old or old TEMPOL donors.