title: C5b-9 terminal complement complex assembly on apoptotic cells in human arterial wall with atherosclerosis.
abstract: Apoptosis plays an important role in atherosclerosis. The factors regulating this process are not well defined. We examined the relation of apoptotic cells with the terminal complement complex C5b-9 in human atherosclerotic lesions. The extent of apoptosis was determined using TdT dUTP nick-end labeling (TUNEL) and immunohistochemistry of apoptosis regulators caspase-3, caspase-9, Bax, and Bcl-2. C5b-9 was localized by immunohistochemistry and immunoelectron microscopy. The apoptotic index was higher in fibrous plaques when compared with intimal fatty streaks and intimal thickenings. Bax expression was present in TUNEL+ apoptotic cells, and Bcl-2 was rarely present in the atherosclerotic wall. Active caspase 9 and caspase 3 deposits were present in the same areas, suggesting an involvement of the mitochondrial pathway. C5b-9 deposits colocalized with TUNEL+ cells, and the percent of double-positive cells was 2% in fatty streaks, 12% in intimal thickenings, and 35% in fibrous plaques. Colocalization of apoptotic cells with C5b-9 was also confirmed by immunoelectron microscopy. In conclusion, some apoptotic cells carry C5b-9 deposits, suggesting that complement might be activated by apoptotic cells and involved in the promotion of apoptosis, contributing to the progression of atherosclerotic lesions.
authors.affiliation: Department of Pathology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Florin
authors.initials: F
authors.lastname: Niculescu
authors.forename: Teodora
authors.initials: T
authors.lastname: Niculescu
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
mesh_terms: D001011:Aorta / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D001161:Arteriosclerosis / Q000378:metabolism*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D005263:Femoral Artery / Q000378:metabolism / Q000648:ultrastructure; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D015938:Complement Membrane Attack Complex; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases