title: Human carotid atherosclerotic plaque protein(s) change HDL protein(s) composition and impair HDL anti-oxidant activity.
abstract: High density lipoprotein (HDL) anti-atherogenic functions are closely associated with cardiovascular disease risk factor, and are dictated by its composition, which is often affected by environmental factors. The present study investigates the effects of the human carotid plaque constituents on HDL composition and biological functions. To this end, human carotid plaques were homogenized and incubated with HDL. Results showed that after incubation, most of the apolipoprotein A1 (Apo A1) protein was released from the HDL, and HDL diameter increased by an average of approximately 2 nm. In parallel, HDL antioxidant activity was impaired. In response to homogenate treatment HDL could not prevent the accelerated oxidation of LDL caused by the homogenate. Boiling of the homogenate prior to its incubation with HDL abolished its effects on HDL composition changes. Moreover, tryptophan fluorescence quenching assay revealed an interaction between plaque component(s) and HDL, an interaction that was reduced by 50% upon using pre-boiled homogenate. These results led to hypothesize that plaque protein(s) interacted with HDL-associated Apo A1 and altered the HDL composition. Immuno-precipitation of Apo A1 that was released from the HDL after its incubation with the homogenate revealed a co-precipitation of three isomers of actin. However, beta-actin alone did not significantly affect the HDL composition, and yet the active protein within the plaque was elusive. In conclusion then, protein(s) in the homogenate interact with HDL protein(s), leading to release of Apo A1 from the HDL particle, a process that was associated with an increase in HDL diameter and with impaired HDL anti-oxidant activity.
authors.affiliation: Department of Oxidative Stress and Human Diseases, MIGAL - Galilee Research Institute, , P.O. Box 831, Kiryat Shmona, 11016, Israel.|Tel-Hai College, Upper Galilee, 12210, Israel.|Lipid Research Laboratory Technion Rappaport Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa, 31096, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Cohen
authors.affiliation: Lipid Research Laboratory Technion Rappaport Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa, 31096, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
authors.affiliation: Department of Oxidative Stress and Human Diseases, MIGAL - Galilee Research Institute, , P.O. Box 831, Kiryat Shmona, 11016, Israel.|Tel-Hai College, Upper Galilee, 12210, Israel.
authors.forename: Soliman
authors.initials: S
authors.lastname: Khatib
authors.affiliation: Lipid Research Laboratory Technion Rappaport Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa, 31096, Israel.
authors.forename: Nina
authors.initials: N
authors.lastname: Volkova
authors.affiliation: Department of Oxidative Stress and Human Diseases, MIGAL - Galilee Research Institute, , P.O. Box 831, Kiryat Shmona, 11016, Israel.|Tel-Hai College, Upper Galilee, 12210, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Vaya
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors
chemical_list: C505693:APOA1 protein, human; D000975:Antioxidants; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL
keywords: Apo A1; HDL; atherosclerosis; plaque; protein