title: Anti-atherosclerotic effects of serelaxin in apolipoprotein E-deficient mice.
abstract: Serelaxin (SLX) is a recombinant form of human relaxin-2, a naturally occurring peptide that regulates maternal cardiovascular adaptations to pregnancy. It is unclear whether SLX has a therapeutic effect on atherosclerosis. Therefore, we investigated direct vascular effects of SLX in a mouse model of atherosclerosis.
  
  
  
  6-8 week-old female apolipoprotein E-deficient mice were fed a high-fat, cholesterol-rich diet for 6 weeks and additionally received a continuous treatment with vehicle or SLX (0.05 or 0.1 μg/h), during the last 4 weeks, via subcutaneously implanted osmotic mini-pumps. Vascular oxidative stress, vasorelaxation and atherosclerotic plaque development were assessed.
  
  
  
  Vascular oxidative stress was reduced in SLX-treated mice (vehicle: 322.67 RLU/s, SLX 0.05 μg/h: 119.76 RLU/s (p < 0.001 vs. vehicle), SLX 0.1 μg/h: 109.33 RLU/s (p < 0.001 vs. vehicle; p = 0.967 vs. 0.05 μg/h SLX)). Further SLX improved endothelium-dependent vasodilatation without influencing endothelium-independent vasorelaxation. Atherosclerotic plaque development was significantly reduced by SLX (vehicle: 0.38 ± 0.02 mm(2), 0.05 μg/h SLX: 0.32 ± 0.02 mm(2) (p = 0.047 vs. vehicle), 0.1 μg/h SLX: 0.29 ± 0.02 mm(2) (p = 0.002 vs. vehicle; p = 0.490 vs. 0.05 μg/h SLX)). Neither vascular macrophage, T-cell or neutrophil infiltration, nor collagen/vascular smooth muscle cell content differed between the groups. We observed a significant down-regulation of the angiotensin II type 1a receptor and a decrease in IL-6 and an increase in IL-10 plasma concentrations.
  
  
  
  Our data demonstrates novel pleiotropic effects of SLX on vascular oxidative stress, endothelial dysfunction and atherosclerotic plaque burden. Therefore, SLX could serve as a new drug for the treatment of atherosclerosis-related diseases.
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany. Electronic address: Vedat.Tiyerili@ukb.uni-bonn.de.
authors.forename: Vedat
authors.initials: V
authors.lastname: Tiyerili
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Beiert
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Schatten
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Bakary
authors.initials: B
authors.lastname: Camara
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Jehle
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Schrickel
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.affiliation: Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
authors.forename: René P
authors.initials: RP
authors.lastname: Andrié
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012065:Relaxin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism; D014664:Vasodilation
chemical_list: C556062:IL10 protein, mouse; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D011994:Recombinant Proteins; C577686:interleukin-6, mouse; C577649:serelaxin protein, human; D016753:Interleukin-10; D012065:Relaxin; D002784:Cholesterol
keywords: Atherosclerosis; Endothelial dysfunction; Serelaxin