title: Association of carotid plaque Lp-PLA(2) with macrophages and Chlamydia pneumoniae infection among patients at risk for stroke.
abstract: BACKGROUND
  We previously showed that the burden of Chlamydia pneumoniae in carotid plaques was significantly associated with plaque interleukin (IL)-6, and serum IL-6 and C-reactive protein (CRP), suggesting that infected plaques contribute to systemic inflammatory markers in patients with stroke risk. Since lipoprotein-associated phospholipase A2 (Lp-PLA(2)) mediates inflammation in atherosclerosis, we hypothesized that serum Lp-PLA(2) mass and activity levels and plaque Lp-PLA(2) may be influenced by plaque C. pneumoniae infection.
  
  
  RESULTS
  Forty-two patients underwent elective carotid endarterectomy. Tissue obtained at surgery was stained by immunohistochemistry for Lp-PLA(2) grade, macrophages, IL-6, C. pneumoniae and CD4+ and CD8+ cells. Serum Lp-PLA(2) activity and mass were measured using the colorimetric activity method (CAM) and ELISA, respectively. Serum homocysteine levels were measured by HPLC. Eleven (26.2%) patients were symptomatic with transient ischemic attacks. There was no correlation between patient risk factors (smoking, coronary artery disease, elevated cholesterol, diabetes, obesity, hypertension and family history of genetic disorders) for atherosclerosis and serum levels or plaque grade for Lp-PLA(2). Plaque Lp-PLA(2) correlated with serum homocysteine levels (p = 0.013), plaque macrophages (p<0.01), and plaque C. pneumoniae (p<0.001), which predominantly infected macrophages, co-localizing with Lp-PLA(2).
  
  
  CONCLUSIONS
  The significant association of plaque Lp-PLA(2) with plaque macrophages and C. pneumoniae suggests an interactive role in accelerating inflammation in atherosclerosis. A possible mechanism for C. pneumoniae in the atherogenic process may involve infection of macrophages that induce Lp-PLA(2) production leading to upregulation of inflammatory mediators in plaque tissue. Additional in vitro and in vivo research will be needed to advance our understanding of specific C. pneumoniae and Lp-PLA(2) interactions in atherosclerosis.
authors.affiliation: Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, USA.
authors.forename: Berna
authors.initials: B
authors.lastname: Atik
authors.forename: S Claiborne
authors.initials: SC
authors.lastname: Johnston
authors.forename: Deborah
authors.initials: D
authors.lastname: Dean
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D002339:Carotid Arteries / Q000201:enzymology*; D002690:Chlamydia Infections / Q000150:complications*; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020521:Stroke / Q000150:complications* / Q000201:enzymology
chemical_list: D006710:Homocysteine; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase