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摘要
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.
- 出版日期2015-6-1
- 单位吉林大学
