Article

Humanin, a Cytoprotective Peptide, Is Expressed in Carotid Artherosclerotic Plaques in Humans

Uppsala University, Sweden
PLoS ONE (Impact Factor: 3.23). 02/2012; 7(2):e31065. DOI: 10.1371/journal.pone.0031065
Source: PubMed

ABSTRACT

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.
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.
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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    • "Further examination of humanin's ability to protect against oxidative stress focused on humanin's potential to help against atherosclerosis . In human carotid atherosclerotic plaques, humanin was found to be twice as high in symptomatic patients compared with asymptomatic, suggesting a role for humanin in atherosclerosis (Zacharias et al. 2012). An in vitro study found that humanin was able to protect endothelial cells from oxidative stress induced by oxidized LDL (Bachar et al. 2010). "

    Full-text · Dataset · Feb 2015
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    • "Circulating humanin levels in humans were recently found to be associated with impaired microvascular coronary endothelial function [16]. HN is highly expressed in unstable carotid plaques in atherosclerotic patients, with higher levels found in symptomatic patients relative to the asymptomatic group [17]. "
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    Preview · Article · Aug 2013 · Biochemical and Biophysical Research Communications
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    • "Further examination of humanin's ability to protect against oxidative stress focused on humanin's potential to help against atherosclerosis . In human carotid atherosclerotic plaques, humanin was found to be twice as high in symptomatic patients compared with asymptomatic, suggesting a role for humanin in atherosclerosis (Zacharias et al. 2012). An in vitro study found that humanin was able to protect endothelial cells from oxidative stress induced by oxidized LDL (Bachar et al. 2010). "
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