title: Renal denervation attenuates progression of atherosclerosis in apolipoprotein E-deficient mice independent of blood pressure lowering.
abstract: The renal autonomic nervous system may contribute to hypertension and vascular disease. Although the effects of renal artery denervation on blood pressure lowering are controversial, there may be other beneficial vascular effects independent of blood pressure lowering. Bilateral renal denervation (RDN) or sham operation (SO) was performed in 14-week-old male apolipoprotein E-deficient mice on a Western diet starting at 10 weeks of age. Efficacy of RDN was confirmed by reduction of renal norepinephrine levels (SO: 3.8±0.1 versus RDN: 1.7±0.3 ng/mL; P<0.01) at 6 weeks after procedure. Compared with SO, RDN had no effect on blood pressure (SO: 101.0±2.4 versus RDN: 97.5±1.6 mm Hg; P=0.25), total cholesterol (SO: 536.7±28.5 versus RDN: 535.7±62.9 mg/dL; P=0.99), or triglycerides (SO: 83.7±3.5 versus RDN: 86.9±10.2 mg/dL; P=0.78). Quantification of atherosclerosis at 20 weeks of age demonstrated reduced atherosclerosis in mice receiving RDN compared with SO (arterial tree oil-red-O surface staining RDN: 4.2±0.5% versus SO: 6.3±0.7%; P<0.05). Reduced atherosclerosis was associated with increased smooth muscle cell content in atherosclerotic plaques (RDN: 13.3±2.1 versus SO: 8.1±0.6%; P<0.05). Serum levels of aldosterone, monocyte chemoattractant protein-1, and 8-isoprostane were lower in mice that received RDN compared with sham-operated mice (aldosterone; RDN: 206.8±33.2 versus SO: 405.5±59.4 pg/mL, P<0.05; monocyte chemoattractant protein-1; RDN: 51.7±7.9 versus SO: 91.71±4.6 pg/mL, P<0.05; 8-isoprostane; RDN: 331.9±38.2 versus SO: 468.5±42.0 pg/mL, P<0.05). RDN reduces progression of atherosclerosis in apolipoprotein E-deficient mice. These changes are associated with reduced aldosterone levels, monocyte chemoattractant protein-1, and markers of oxidative stress.
authors: From the Cardiovascular Research Center, Department of Internal Medicine, University of Michigan, Ann Arbor.
authors: Hui
authors: H
authors: Wang
authors: From the Cardiovascular Research Center, Department of Internal Medicine, University of Michigan, Ann Arbor.
authors: Jintao
authors: J
authors: Wang
authors: From the Cardiovascular Research Center, Department of Internal Medicine, University of Michigan, Ann Arbor.
authors: Chiao
authors: C
authors: Guo
authors: From the Cardiovascular Research Center, Department of Internal Medicine, University of Michigan, Ann Arbor.
authors: Wei
authors: W
authors: Luo
authors: From the Cardiovascular Research Center, Department of Internal Medicine, University of Michigan, Ann Arbor.
authors: Kyle
authors: K
authors: Kleiman
authors: From the Cardiovascular Research Center, Department of Internal Medicine, University of Michigan, Ann Arbor. deitzman@umich.edu.
authors: Daniel T
authors: DT
authors: Eitzman
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency*; D050197:Atherosclerosis / Q000097:blood / Q000503:physiopathology / Q000601:surgery*; D001795:Blood Pressure Determination; D018932:Chemokine CCL2 / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D006973:Hypertension / Q000097:blood / Q000503:physiopathology / Q000601:surgery*; D007668:Kidney; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D013562:Sympathectomy / Q000379:methods*
chemical_list: D001057:Apolipoproteins E; D018932:Chemokine CCL2; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost
keywords: atherosclerosis; hypertension; oxidative stress; sympathetic nervous system
references: Eur Heart J. 2013 Jul;34(28):2149-57
references: 23620497
references: Br J Haematol. 2013 Jul;162(1):120-9
references: 23590132
references: J Am Heart Assoc. 2013 Oct;2(5):e000375
references: 24125845
references: N Engl J Med. 2014 Apr 10;370(15):1393-401
references: 24678939
references: Eur Heart J. 2014 Jul;35(26):1706-11
references: 24829361
references: Circulation. 2002 May 7;105(18):2212-6
references: 11994257
references: Prog Brain Res. 2000;122:351-67
references: 10737070
references: J Clin Hypertens (Greenwich). 2014 Aug;16(8):599-605
references: 25039997
references: J Cardiovasc Pharmacol. 2003 Jun;41(6):955-63
references: 12775976
references: Circulation. 2004 May 11;109(18):2213-20
references: 15123520
references: Hypertension. 1998 Aug;32(2):249-54
references: 9719050
references: J Am Med Assoc. 1953 Aug 15;152(16):1501-4
references: 13061307
references: Hypertension. 2005 Nov;46(5):1135-9
references: 16203870
references: J Am Soc Nephrol. 2006 May;17(5):1362-72
references: 16571782
references: Hypertension. 2007 Sep;50(3):547-56
references: 17646575
references: Physiol Rev. 2010 Apr;90(2):513-57
references: 20393193
references: Circ Res. 2010 Aug 20;107(4):540-8
references: 20558825
references: Circulation. 2011 May 10;123(18):1940-6
references: 21518978
references: Atherosclerosis. 2012 Jan;220(1):110-7
references: 22041028
references: J Am Coll Cardiol. 2012 Mar 6;59(10):901-9
references: 22381425
references: Diabetes. 2012 Dec;61(12):3219-27
references: 22891216
references: Compr Physiol. 2011 Apr;1(2):731-67
references: 23737201
references: J Am Heart Assoc. 2013 Aug;2(4):e000197
references: 23974905