title: Aortic perivascular adipose-derived interleukin-6 contributes to arterial stiffness in low-density lipoprotein receptor deficient mice.
abstract: 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.
authors.affiliation: Department of Cardiology, The First Hospital of Jilin University, Changchun, China;
authors.forename: Bing
authors.initials: B
authors.lastname: Du
authors.affiliation: Kinesiology and Health Promotion, University of Kentucky, Lexington, Kentucky.
authors.forename: An
authors.initials: A
authors.lastname: Ouyang
authors.affiliation: Department of Integrative Physiology, University of Colorado, Boulder, Colorado; and.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Eng
authors.affiliation: Kinesiology and Health Promotion, University of Kentucky, Lexington, Kentucky Bradley.fleenor@uky.edu.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Fleenor
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D063177:Pulse Wave Analysis; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D059289:Vascular Stiffness
chemical_list: D024042:Collagen Type I; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D011973:Receptors, LDL
keywords: aorta; cholesterol; inflammation; periaortic fat; triglycerides
references.citation: J Am Heart Assoc. 2012 Dec;1(6):e004200
references.pmid: 23316328
references.citation: Circ Res. 2009 Feb 27;104(4):541-9
references.pmid: 19122178
references.citation: J Mol Cell Cardiol. 2013 Apr;57:1-12
references.pmid: 23333801
references.citation: Arterioscler Thromb Vasc Biol. 2013 Apr;33(4):839-46
references.pmid: 23413430
references.citation: Am J Hypertens. 2013 May;26(5):608-16
references.pmid: 23449607
references.citation: J Gerontol A Biol Sci Med Sci. 2013 Jul;68(7):780-92
references.pmid: 23213032
references.citation: Obesity (Silver Spring). 2013 Jul;21(7):1496-503
references.pmid: 23754461
references.citation: Int J Cardiol. 2013 Oct 3;168(3):2397-403
references.pmid: 23452887
references.citation: Circulation. 2014 Jan 21;129(3):e28-e292
references.pmid: 24352519
references.citation: J Am Coll Cardiol. 2014 Feb 25;63(7):636-46
references.pmid: 24239664
references.citation: Aging Cell. 2014 Jun;13(3):576-8
references.pmid: 24341314
references.citation: Circulation. 2014 Jun 10;129(23):2403-13
references.pmid: 24710030
references.citation: Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1827-30
references.pmid: 25012133
references.citation: Am J Physiol Heart Circ Physiol. 2014 Oct 15;307(8):H1252-61
references.pmid: 25128168
references.citation: Int J Obes (Lond). 2014 Nov;38(11):1397-402
references.pmid: 24525960
references.citation: Eur J Cardiovasc Prev Rehabil. 2004 Dec;11(6):497-502
references.pmid: 15580061
references.citation: Can J Appl Physiol. 2003 Apr;28(2):204-12
references.pmid: 12825330
references.citation: J Vis Exp. 2009;(27). pii: 1291. doi: 10.3791/1291
references.pmid: 19488026
references.citation: Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1458-64
references.pmid: 19608970
references.citation: J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27
references.pmid: 20338492
references.citation: BMC Med. 2011;9:25
references.pmid: 21410966
references.citation: Eur J Clin Invest. 2011 Sep;41(9):929-36
references.pmid: 21314825
references.citation: Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2402-9
references.pmid: 21885847
references.citation: J Biol Chem. 2012 Jan 20;287(4):2666-77
references.pmid: 22157761
references.citation: Aging Cell. 2012 Apr;11(2):269-76
references.pmid: 22168264
references.citation: Gerontology. 2012;58(3):227-37
references.pmid: 22222677
references.citation: Exp Gerontol. 2012 Aug;47(8):565-72
references.pmid: 22569357
references.citation: Exp Gerontol. 2012 Aug;47(8):588-94
references.pmid: 22588062
references.citation: Atherosclerosis. 2012 Aug;223(2):314-20
references.pmid: 22770991
references.citation: Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15888-93
references.pmid: 22908267
references.citation: Am J Physiol Endocrinol Metab. 2012 Oct 15;303(8):E1061-8
references.pmid: 22932781
references.citation: Am J Physiol Heart Circ Physiol. 2000 Feb;278(2):H428-34
references.pmid: 10666072
references.citation: Biochem Pharmacol. 2000 Oct 15;60(8):1185-95
references.pmid: 11007957
references.citation: Circulation. 2001 Jan 23;103(3):448-54
references.pmid: 11157699
references.citation: J Am Coll Cardiol. 2002 Mar 20;39(6):1005-11
references.pmid: 11897443
references.citation: Eur J Clin Invest. 2004 May;34(5):335-41
references.pmid: 15147330
references.citation: Arterioscler Thromb Vasc Biol. 2005 May;25(5):932-43
references.pmid: 15731494
references.citation: Am J Physiol Heart Circ Physiol. 2005 Sep;289(3):H1209-17
references.pmid: 15863465
references.citation: Adv Cardiol. 2007;44:76-95
references.pmid: 17075200
references.citation: Eur J Clin Invest. 2007 Mar;37(3):197-206
references.pmid: 17359487
references.citation: Hypertension. 2008 Jun;51(6):1651-7
references.pmid: 18426996
references.citation: Exp Gerontol. 2013 Feb;48(2):269-76
references.pmid: 23142245