Low-density lipoprotein receptor-deficient mice exhibited increased aortic pulse wave velocity (407 vs. 353 cm/s) and intrinsic mechanical stiffness mediated by PVAT-derived IL-6 secretion.
PVAT-derived IL-6 contributes to aortic stiffness and remodeling in LDLr(-/-) mice, highlighting a potential therapeutic target for vascular stiffness.
Absolute Event Rate: 407% vs 353%
p-value: p=<0.05
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.
Du et al. (Sat,) conducted a other in Arterial stiffness and hypercholesterolemia. Low-density lipoprotein receptor deficiency (LDLr-/-) vs. Wild-type (WT) mice was evaluated on Aortic pulse wave velocity (aPWV) (p=<0.05). Low-density lipoprotein receptor-deficient mice exhibited increased aortic pulse wave velocity (407 vs. 353 cm/s) and intrinsic mechanical stiffness mediated by PVAT-derived IL-6 secretion.