Elsevier

Atherosclerosis

Volume 158, Issue 1, September 2001, Pages 73-79
Atherosclerosis

Demonstration of Chlamydia pneumoniae in atherosclerotic arteries from various vascular regions

https://doi.org/10.1016/S0021-9150(01)00411-7Get rights and content

Abstract

Chlamydia pneumoniae (CP) has been reported to be a pathogenic agent in the mechanism leading to atherosclerosis. The majority of available data is focused mainly on coronary artery disease whereas the distribution of CP in different areas, associated with atherosclerotic disorders, has not been completely clarified. In this study we investigated the presence of CP in atheromasic plaques from five different vascular areas (basilary artery, coronary artery, thoracic aorta, abdominal aorta, renal arteries) using nested polymerase chain reaction (PCR) and immunohistochemical staining (IHC), in order to establish the putative association of CP with atherosclerotic disease. The same atheromasic plaques were also tested for the presence of Helicobacter pylori (HP) and cytomegalovirus (CMV), other putative agents of atherosclerosis, using a nested PCR technique. Our data indicate that the presence of CP can be demonstrated in 100% of patients tested, considering globally the five areas of analysis. On the other hand the presence of HP has been demonstrated in four out of 18 patients (22.2%), and CMV only in three out of 18 (16.6%). Our results strongly suggest an association between CP and atherosclerosis and highlight the need for the detection of CP in multiple vascular areas of the same patient.

Introduction

Chlamydia pneumoniae (CP), an obligate intracellular Gram-negative bacterium, is involved in a wide spectrum of symptomatic respiratory tract diseases (pneumonia, bronchitis and sinusitis); however, 70% of infections are asymptomatic. Antibodies against CP are present in 50–70% of the adult population suggesting that the majority of people are infected and re-infected throughout their lives [1]. Saikku et al. [2] demonstrated higher levels of antibody to CP in patients with acute myocardial infarction and chronic coronary heart disease than in randomly selected controls. More recently, the association between CP infection and coronary artery disease has been confirmed by seroepidemiologic studies [3], [4], [5]; direct detection of the organism in atherosclerotic plaques by electron microscopy (TEM), immunohistochemical staining (IHC) and polymerase chain reaction PCR [6], [7]. Other serological studies suggest a relationship between atherosclerosis and either Cytomegalovirus (CMV) or Helicobacter pylori (HP) [8]. Taylor-Robinson and Thomas [9], summarizing the results on this association obtained from 23 studies, showed that the demonstration of CP in various arteries was in the 14–71% range, with a total average of 42%. Moreover, Tiran et al. [10], observed that percutaneous transluminal angioplasty induced a significant rise in CP specific antibodies, suggesting that microbial antigens already present, which could be released and/or exposed from within the plaque, may induce a secondary or memory immune response. In addition, other recent studies have supported CP being implicated in atherosclerotic disease [11], [12], [13], and treatment with specific antibiotics has been reported to reduce the risk of recurrent cardiac events in patients with atherosclerotic coronary heart disease [14], [15]. In some cases, high serological levels of antibodies against CMV and HP are associated with atherosclerosis, but their direct role remains questionable in atherosclerotic lesions [16], [17], [18].

In the present study, using IHC and PCR techniques, the presence of CP, HP and CMV, was investigated in atheroma specimens from different anatomic regions (basilary artery, coronary artery, thoracic aorta, abdominal aorta, renal arteries) of 18 autopsy cases. The aim of our study was to establish the presence of the above mentioned agents in atheromasic lesions.

Section snippets

Autopsy specimens

Twelve men and six women, ranging from 48 to 91 years of age and with no history of recent respiratory disease, underwent autopsy 16–30 h after death. The causes of death were coronary heart disease (ten cases), pulmonary thromboembolism (five cases), pleuropericarditis (one case), aortic rupture (two cases) (Table 1).

Autopsy atherosclerotic tissue specimens were obtained from the basilary artery, the left descending coronary artery, the thoracic aorta, the abdominal aorta and the renal

Results

Using the PCR technique the presence of CP DNA was demonstrated in all the patients examined with a positivity ranging from two to five sites in each patient (Table 3). On the other hand, the patients positive for atherosclerotic plaques (ATS) were positive for HP and CMV 4/18 (22.2%) and 3/18 (16.6%), respectively. Taken together, among the 90 cardiovascular samples examined, CP was detected in 69 (69.8%), HP in six (0.07%) and CMV in three (0.03%). Interestingly, in the nine cerebral

Discussion

In this study we have demonstrated that, by analyzing five different vascular areas from each patient, the detection of CP in atherosclerotic patients resulted in 100% positivity. The presence of CP was demonstrated at least in two of the areas with the PCR technique and in at least one by the IHC technique (Table 4). Combining the two techniques (PCR and IHC), the percentage of positivity for a single area was higher than that obtained using each technique separately. A multiple site analysis

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