Aortic perivascular adipose-derived interleukin-6 contributes to arterial stiffness in low-density lipoprotein receptor deficient mice

We tested the hypothesis that aortic perivascular adipose tissue (PVAT) from young low-density lipoprotein receptor-deficient (LDLr−/−) mice promotes aortic stiffness and remodeling, which would be mediated by greater PVAT-derived IL-6 secretion. Arterial stiffness was assessed by aortic pulse wave velocity and with ex vivo intrinsic mechanical properties testing in young (4–6 mo old) wild-type (WT) and LDLr−/− chow-fed mice. Compared with WT mice, LDLr−/− mice had increased aortic pulse wave velocity (407 ± 18 vs. 353 ± 13 cm/s) and intrinsic mechanical stiffness (5,308 ± 623 vs. 3,355 ± 330 kPa) that was associated with greater aortic protein expression of collagen type I and advanced glycation end products (all P < 0.05 vs. WT mice). Aortic segments from LDLr−/− compared with WT mice cultured in the presence of PVAT had greater intrinsic mechanical stiffness (6,092 ± 480 vs. 3,710 ± 316 kPa), and this was reversed in LDLr−/− mouse arteries cultured without PVAT (3,473 ± 577 kPa, both P < 0.05). Collagen type I and advanced glycation end products were increased in LDLr−/− mouse arteries cultured with PVAT ( P < 0.05 vs. WT mouse arteries), which was attenuated when arteries were cultured in the absence of PVAT ( P < 0.05). PVAT from LDLr−/− mice secreted larger amounts of IL-6 (3.4 ± 0.1 vs. 2.3 ± 0.7 ng/ml, P < 0.05), and IL-6 neutralizing antibody decreased intrinsic mechanical stiffness in LDLr−/− aortic segments cultured with PVAT ( P < 0.05). Collectively, these data provide evidence for a role of PVAT-derived IL-6 in the pathogenesis of aortic stiffness and remodeling in chow-fed LDLr−/− mice.