Superoxide signaling in perivascular adipose tissue promotes age‐related artery stiffness

• Published in: Aging cell Vol. 13; no. 3; pp. 576 - 578
• Main Authors: Fleenor, Bradley S., Eng, Jason S., Sindler, Amy L., Pham, Bryant T., Kloor, Jackson D., Seals, Douglas R.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-06-2014; BlackWell Publishing Ltd
• Subjects: Adipose Tissue - metabolism; Age Factors; Animals; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - pathology; fat; Male; Mice; Mice, Inbred C57BL; oxidative stress; peri‐aortic; Short Takes; Signal Transduction; Superoxides - metabolism; TEMPOL; Vascular Stiffness - physiology; fat; TEMPOL; oxidative stress; peri-aortic
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.12196

Summary
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.