title: Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice.
abstract: OBJECTIVE
  Humanin (HN) is a cytoprotective peptide derived from endogenous mitochondria, expressed in the endothelial layer of human vessels, but its role in atherogenesis in vivo is not known. In vitro study, however, HN reduced oxidized low-density lipoprotein induced formation of reactive oxygen species and apoptosis. The present study tested the hypothesis that long term treatment with HN will have a protective role against endothelial dysfunction and progression of atherosclerosis in vivo.
  
  
  RESULTS
  Daily intraperitonial injection of the HN analogue HNGF6A for 16 weeks prevented endothelial dysfunction and decreased atherosclerotic plaque size in the proximal aorta of ApoE-deficient mice fed on a high cholesterol diet, without showing direct vasoactive effects or cholesterol-reducing effects. HN was expressed in the endothelial layer on the aortic plaques. HNGF6A treatment reduced apoptosis and nitrotyrosine immunoreactivity in the aortic plaques without affecting the systemic cytokine profile. HNGF6A also preserved expression of endothelial nitric oxide synthase in aorta.
  
  
  CONCLUSIONS
  HN may have a protective effect on endothelial function and progression of atherosclerosis by modulating oxidative stress and apoptosis in the developing plaque.
authors.affiliation: Department of Internal Medicine, Divisions of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States.
authors.forename: Yun K
authors.initials: YK
authors.lastname: Oh
authors.forename: Adi R
authors.initials: AR
authors.lastname: Bachar
authors.forename: David G
authors.initials: DG
authors.lastname: Zacharias
authors.forename: Sung Gyun
authors.initials: SG
authors.lastname: Kim
authors.forename: Junxiang
authors.initials: J
authors.lastname: Wan
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Cobb
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000517:prevention & control; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006937:Hypercholesterolemia / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000517:prevention & control*
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D047908:Intracellular Signaling Peptides and Proteins; C427211:humanin