Humanin, a cytoprotective peptide, is expressed in carotid artherosclerotic plaques in humans

David G. Zacharias, Sung Gyun Kim, Alfonso Eirin, Adi R. Bachar, Yun K. Oh, Joerg Herrmann, Martin G Rodriguez-Porcel, Pinchas Cohen, Lilach O Lerman, Amir Lerman

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objective: The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN) is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques. Methods and Results: Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001). These data were further confirmed by immunoblot (density of HN/β-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01). TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01). Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization), smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9. Conclusions: The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque.

Original languageEnglish (US)
Article numbere31065
JournalPLoS One
Volume7
Issue number2
DOIs
StatePublished - Feb 6 2012

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peptides
Peptides
Atherosclerotic Plaques
dendritic cells
atherosclerosis
smooth muscle
myocytes
fluorescent antibody technique
fibroblasts
actin
microscopy
macrophages
oxidative stress
apoptosis
history
Oxidative stress
Carotid Endarterectomy
Macrophages
In Situ Nick-End Labeling
Fibroblasts

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Humanin, a cytoprotective peptide, is expressed in carotid artherosclerotic plaques in humans. / Zacharias, David G.; Kim, Sung Gyun; Eirin, Alfonso; Bachar, Adi R.; Oh, Yun K.; Herrmann, Joerg; Rodriguez-Porcel, Martin G; Cohen, Pinchas; Lerman, Lilach O; Lerman, Amir.

In: PLoS One, Vol. 7, No. 2, e31065, 06.02.2012.

Research output: Contribution to journalArticle

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abstract = "Objective: The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN) is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques. Methods and Results: Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13{\%} of plaque area, p<0.0001). These data were further confirmed by immunoblot (density of HN/β-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01). TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46{\%} of nuclei, p<0.01). Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization), smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9. Conclusions: The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque.",
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