title: Distinctive proteomic profiles among different regions of human carotid plaques in men and women.
abstract: The heterogeneity of atherosclerotic tissue has limited comprehension in proteomic and metabolomic analyses. To elucidate the functional implications, and differences between genders, of atherosclerotic lesion formation we investigated protein profiles from different regions of human carotid atherosclerotic arteries; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Proteomic analysis was performed using 2-DE with MALDI-TOF, with validation using nLC-MS/MS. Protein mapping of 2-DE identified 52 unique proteins, including 15 previously unmapped proteins, of which 41 proteins were confirmed by nLC-MS/MS analysis. Expression levels of 18 proteins were significantly altered in plaque regions compared to the internal control region. Nine proteins showed site-specific alterations, irrespective of gender, with clear associations to extracellular matrix remodelling. Five proteins display gender-specific alterations with 2-DE, with two alterations validated by nLC-MS/MS. Gender differences in ferritin light chain and transthyretin were validated using both techniques. Validation of immunohistochemistry confirmed significantly higher levels of ferritin in plaques from male patients. Proteomic analysis of different plaque regions has reduced the effects of plaque heterogeneity, and significant differences in protein expression are determined in specific regions and between genders. These proteomes have functional implications in plaque progression and are of importance in understanding gender differences in atherosclerosis.
authors.affiliation: Occupational and Environmental Medicine Center, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Wenzhao
authors.initials: W
authors.lastname: Liang
authors.affiliation: Occupational and Environmental Medicine Center, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Division of Obstetrics and Gynaecology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Ward
authors.affiliation: Occupational and Environmental Medicine Center, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Helen
authors.initials: H
authors.lastname: Karlsson
authors.affiliation: Occupational and Environmental Medicine Center, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Ljunggren
authors.affiliation: Division of Obstetrics and Gynaecology, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Lindahl
authors.affiliation: Occupational and Environmental Medicine Center, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Yuan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001052:Apoferritins / Q000032:analysis; D016893:Carotid Stenosis / Q000473:pathology*; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000032:analysis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D011228:Prealbumin; D020543:Proteome; D001052:Apoferritins