Expression of Secretory Group IIA Phospholipase A ₂ in Relation to the Presence of Microbial Agents, Macrophage Infiltrates, and Transcripts of Proinflammatory Cytokines in Human Aortic Tissues

Abstract

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 A 2 (sPLA 2 -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 sPLA 2 -IIA was studied immunohistochemically by using monoclonal antibodies against human sPLA 2 -IIA. Transcripts specific for sPLA 2 -IIA, interleukin-1␤, 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 sPLA 2 -IIA. Pathogens as well as sPLA 2 -IIA and cytokines were found to be present not only in advanced but also in early stages of atherosclerosis. In tissues negative for sPLA 2 -IIA and cytokine expression, none of the pathogens could be identified. Because macrophages exposed to phospholipase A 2 -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.

Expression of secreted phospholipase A2-Group IIA correlates with prognosis of gastric adenocarcinoma

“…The present study additionally identified that sPLA2-II expression in gastric adenocarcinoma was associated with H. pylori infection. The results of the present study are supported by those of previous studies (17)(18)(19). These previous studies suggested that H. pylori infection may be associated with gastric cancer, and H. pylori has subsequently been identified as a World Health Organization class I carcinogen (20).…”

Lipolysis of LDL by Human Secretory Phospholipase A 2 Induces Particle Fusion and Enhances the Retention of LDL to Human Aortic Proteoglycans

“…Because the arterial intima has been shown to contain snpPLA 2 , [22][23][24][25][26] and both LDL-like particles and lipid droplets 10,43 isolated from atherosclerotic lesions show signs of phospholipid hydrolysis, we suggest that the present results can be extrapolated to the actual events in the arterial intima. snpPLA 2 is found in the intimas of even early atherosclerotic lesions 24 -26 and is occasionally found in nonatherosclerotic intimas containing considerable macrophage infiltration.…”

“…26 The enzyme is able to bind to arterial PGs 21 and was found in the arterial intima in association with extracellular matrix components. 24 Most importantly, snpPLA 2 has also been found in contact with extracellular lipid droplets.…”

“…snpPLA 2 is found in the intimas of even early atherosclerotic lesions 24 -26 and is occasionally found in nonatherosclerotic intimas containing considerable macrophage infiltration. 26 The enzyme is able to bind to arterial PGs 21 and was found in the arterial intima in association with extracellular matrix components. 24 Most importantly, snpPLA 2 has also been found in contact with extracellular lipid droplets.…”

“…Recently, type II secretory nonpancreatic phospholipase A 2 (snpPLA 2 ), which is capable of lipolyzing LDL, 21 has been shown to be located in both atherosclerotic and nonatherosclerotic arterial intima [22][23][24][25][26] and to be associated with extracellular matrix structures and lipid droplets. 24 Interestingly, lipolysis of LDL by bee venom PLA 2 reduces the size of the LDL particles in the absence of glycosaminoglycans (GAGs) 17,20,27 but increases their size in the presence of heparin-GAG.…”