Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice

Yun K. Oh, Adi R. Bachar, David G. Zacharias, Sung Gyun Kim, Junxiang Wan, Laura J. Cobb, Lilach O. Lerman, Pinchas Cohen, Amir Lerman

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalAtherosclerosis
Volume219
Issue number1
DOIs
StatePublished - Nov 2011

Keywords

  • ApoE-deficient mice
  • Atherosclerosis
  • Endothelial dysfunction
  • Humanin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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