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 language | English (US) |
|---|---|
| Article number | e31065 |
| Journal | PLoS One |
| Volume | 7 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 6 2012 |
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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 journal › Article
}
TY - JOUR
T1 - Humanin, a cytoprotective peptide, is expressed in carotid artherosclerotic plaques in humans
AU - Zacharias, David G.
AU - Kim, Sung Gyun
AU - Eirin, Alfonso
AU - Bachar, Adi R.
AU - Oh, Yun K.
AU - Herrmann, Joerg
AU - Rodriguez-Porcel, Martin G
AU - Cohen, Pinchas
AU - Lerman, Lilach O
AU - Lerman, Amir
PY - 2012/2/6
Y1 - 2012/2/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84856656873&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856656873&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0031065
DO - 10.1371/journal.pone.0031065
M3 - Article
C2 - 22328926
AN - SCOPUS:84856656873
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e31065
ER -