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

First Author  Du B Year  2015
Journal  Am J Physiol Heart Circ Physiol Volume  308
Issue  11 Pages  H1382-90
PubMed ID  25840831 Mgi Jnum  J:224652
Mgi Id  MGI:5688463 Doi  10.1152/ajpheart.00712.2014
Citation  Du B, et al. (2015) Aortic perivascular adipose-derived interleukin-6 contributes to arterial stiffness in low-density lipoprotein receptor deficient mice. Am J Physiol Heart Circ Physiol 308(11):H1382-90
abstractText  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.
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