Humanin, a Cytoprotective Peptide, Is Expressed in Carotid Artherosclerotic Plaques in Humans |
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Authors: | David G Zacharias Sung Gyun Kim Alfonso Eirin Massat Adi R Bachar Yun K Oh Joerg Herrmann Martin Rodriguez-Porcel Pinchas Cohen Lilach O Lerman Amir Lerman |
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Institution: | 1. Division of Cardiovascular Diseases, Department of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.; 2. Department of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.; 3. Department of Pediatrics, Division of Endocrinology, Mattel Children''s Hospital, University of California, Los Angeles, Los Angeles, California, United States of America.;Uppsala University, Sweden |
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Abstract: | ObjectiveThe 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 ResultsPlaque 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.ConclusionsThe 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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