Multiple infections in carotid atherosclerotic plaques

Chlamydia pneumoniae, cytomegalovirus, herpes simplex virus, and recently, periodontal disease, have been associated with human atherosclerosis. Porphyromonas gingivalis and Streptococcus sanguis are major pathogens associated with periodontitis, a common chronic inflammatory condition in adults. Investigators have found that these infectious agents may influence vascular cell functions by inducing thrombus formation, vascular cell proliferation, apoptosis, and cell death.

The main purpose of our study was to investigate the relation between the presence of multiple infectious agents in human carotid endarterectomy specimens and pathoanatomic features of the corresponding carotid plaques. Histologically, plaque rupture of the fibrous cap and communication of the luminal thrombus with the central necrotic lipid core was seen in or at proximity to the macrophage-rich shoulder (unstable plaque region). Thrombus within the lipid core without plaque rupture was occasionally found near the internal elastic lamina, associated with increased vascularity and lymphocytic infiltrate. Apoptosis, as detected by both the immunohistochemical staining of apoptosis-related proteins and in situ labeling of internucleosomally degraded DNA, was common in atherosclerotic plaques. Immunostainings for C pneumoniae, cytomegalovirus, herpes simplex virus-1, P gingivalis, and S sanguis were positive in the carotid plaques. From 1 to 4 organisms were found in the same specimen. The micro-organisms were immunolocalized in plaque shoulders and lymphohistiocytic infiltrate, associated with ulcer and thrombus formation, and adjacent to areas of strong labeling for apoptotic bodies.

Our data provide evidence that multiple infectious agents may be found in atherosclerotic plaques, and sometimes in the same specimen. The current study is the first to report the detection of 2 major odontopathogens, P gingivalis and S sanguis, in atherosclerotic plaques. The immunolocalization of these micro-organisms within unstable plaque regions and their association with plaque ulceration, thrombosis, and apoptosis in vascular cells are intriguing. Multiple infectious agents may alter vascular cell function and provide a "trigger" for acute ischemic stroke events. Further evidence from human studies and animal models will be needed.