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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:751.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Expression of Secretory Group IIA Phospholipase A₂ in Relation to the Presence of Microbial Agents, Macrophage Infiltrates, and Transcripts of Proinflammatory Cytokines in Human Aortic Tissues

Presented as a preliminary report at the 71st Scientific Sessions of the American Heart Association, Dallas, Tex, November 8–11, 1998.

Mario Menschikowski; Andrea Rosner-Schiering; Rolf Eckey; Erich Mueller; Rainer Koch; Werner Jaross

From the Institut für Klinische Chemie und Laboratoriumsmedizin (M.M., A.R.-S., R.E., W.J.), the Institut für Informatik und Biometrie (R.K.), and the Institut für Rechtsmedizin (E.M.), Technische Universität Dresden, Medizinische Fakultät "Carl Gustav Carus," Dresden, Germany.

Correspondence to Mario Menschikowski, PhD, Institut für Klinische Chemie und Laboratoriumsmedizin, Technische Universität Dresden, Medizinische Fakultät "Carl Gustav Carus," Fetscherstrasse 74, D-01307 Dresden, Germany. E-mail menschik{at}rcs.urz.tu-dresden.de

Abstract—Recent seroepidemiological and immunohistochemical studies have demonstrated an association between microbial infections and atherosclerosis. However, the mechanisms underlying this association are widely unknown. In the present study, arterial specimens obtained at autopsy after sudden death were analyzed concerning (1) the presence of Chlamydia pneumoniae, cytomegalovirus, herpes simplex virus, and Helicobacter pylori; (2) the expression of secretory group IIA phospholipase A₂ (sPLA₂-IIA) and of proinflammatory cytokines; and (3) the stage of atherosclerosis. Genomic DNA of microbial pathogens was determined by the polymerase chain reaction technique. The expression of sPLA₂-IIA was studied immunohistochemically by using monoclonal antibodies against human sPLA₂-IIA. Transcripts specific for sPLA₂-IIA, interleukin-1ß, tumor necrosis factor-, and interferon- were identified by reverse transcription–polymerase chain reaction. In 18 of 102 analyzed specimens, DNA of microbial pathogens was found. Thirteen sections were positive for C pneumoniae, whereas 2 specimens were positive either for cytomegalovirus or for herpes simplex virus. One section contained genomic DNA of all 3 pathogens simultaneously. None of the analyzed tissues exhibited nucleic acids specific for H pylori. In addition to macrophage infiltrates, the presence of microbial DNA was closely associated with the occurrence of transcripts specific for proinflammatory cytokines and sPLA₂-IIA. Pathogens as well as sPLA₂-IIA and cytokines were found to be present not only in advanced but also in early stages of atherosclerosis. In tissues negative for sPLA₂-IIA and cytokine expression, none of the pathogens could be identified. Because macrophages exposed to phospholipase A₂–treated lipoproteins are transformed into foam cells in vitro, the results of this study suggest an alternative mechanism by which microbial infections may act in a proatherogenic fashion in vessel walls.

Key Words: infections • secretory phospholipase A₂ • inflammation • atherosclerosis

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