Detection of Chlamydia pneumoniae in human nonrheumatic stenotic aortic valves.

OBJECTIVES: We sought to study the possible presence of Chlamydia pneumoniae in aortic valve stenosis (AVS). BACKGROUND: Inflammation and immune mechanisms are considered important for the pathogenesis of nonrheumatic AVS. All chlamydial species are able to cause heart infections, and seroepidemiologic studies have indicated an association between chronic C. pneumoniae infection and coronary artery disease. Furthermore, the organism has been demonstrated in atherosclerotic lesions. METHODS: Aortic valve specimens with varying degrees of macroscopic disease were obtained from 35 subjects--17 consecutive patients undergoing aortic valve replacement for treatment of nonrheumatic AVS and 18 age-matched subjects at autopsy. The possible presence of C. pneumoniae in aortic valves was studied by immunohistochemical analysis, polymerase chain reaction or transmission electron microscopy, or a combination of these. RESULTS: Positive immunohistochemical staining with C. pneumoniae specific antibody was found in 9 (53%) of 17 patients with advanced aortic valve disease requiring surgical treatment (group A), 8 (80%) of 10 cadavers with clearly macroscopic aortic valve pathology (group B) and 1 (12%) of 8 grossly normal cadaver control subjects (group C). Statistical significance with regard to the presence of C. pneumoniae was found when combined diseased subjects (groups A and B: total 17 of 27 subjects) were compared with group C (p = 0.018). However, when group A was compared with group C, there was only marginal statistical significance (p = 0.088). Finally, there was a strong statistical significance (p = 0.015) when groups B and C were compared. Chlamydia pneumoniae DNA was also found in three stenotic valves, and in two of the three tested valve specimens chlamydia-like particles were seen by electron microscopy. CONCLUSIONS: Chlamydia pneumoniae is frequently present in nonrheumatic AVS. Similarly, the high number of C. pneumoniae infections detected in the early lesions of "degenerative" AVS suggest that this pathogen may play an etiologic role in the development of this disease. The validity of this relation requires additional study.

Detection of Chlamydia pneumoniae by colorimetric in situ hybridization.

Chlamydia pneumoniae causes chronic infections, which have been associated with cardiovascular diseases. The antigenic structures of the organism have been detected in atherosclerotic lesions by immunohistochemistry. We wanted to further evaluate the presence and localization of C. pneumoniae in different tissues by in situ hybridization. We established a new colorimetric in situ hybridization method using a digoxigenin-labelled probe and studied the localization of C. pneumoniae in formalin-fixed, paraffin-embedded lungs of infected mice. We also used the method to study its presence in 12 abdominal aortic aneurysms. In C. pneumoniae-infected mice, the organism was first detected in bronchial epithelial cells, and later in pneumocytes and endothelial cells. C. pneumoniae was also present in five of eight abdominal aortic aneurysms previously shown to be positive by immunohistochemistry. The findings are in accordance with the invasive nature of C. pneumoniae, and confirm its presence in abdominal aortic aneurysms.

Animal models for Chlamydia pneumoniae infection.

There is accumulating evidence that persistent Chlamydia pneumoniae infections occur in vivo. Animal studies are necessary in order to evaluate the effects of different treatment regimens for eradication of such infections. A mouse model was found to be efficacious for the study of the effects of cortisone and antimicrobial agents on C. pneumoniae infection.

Chlamydia pneumoniae infection in patients with chronic obstructive pulmonary disease.

The prevalence of chronic Chlamydia pneumoniae infection was assessed in 54 patients with established chronic obstructive pulmonary disease (COPD), 41 of these with severe COPD (group I), 13 with mild to moderate COPD (group II), and in 23 patients with community-acquired pneumonia (controls, group III). Specific IgG and IgA antibody levels and circulating immune complexes (ICs) were measured in paired sera, and specific secretory IgA (sIgA) levels in sputum specimens. A polymerase chain reaction (PCR) test was used for the detection of C. pneumoniae in sputum. According to our definite diagnosis criterion, 65% of the COPD patients showed evidence of suspected chronic C. pneumoniae infection and the prevalence was still higher (71%) in patients with severe disease. The occurrence of specific markers of infection was invariably highest in patients with severe COPD, next-highest in patients with mild to moderate COPD and lowest in pneumonia patients. The association between COPD and C. pneumoniae infection persisted after controlling for the potential confounding factors.

Chlamydia pneumoniae infection in human monocytes.

Chlamydia pneumoniae infection has been associated with cardiovascular diseases in seroepidemiological studies and by demonstration of the pathogen in atherosclerotic lesions. It has the capacity to infect several cell types, including monocyte-derived macrophages, which play an essential role in the development of atherosclerosis. However, the persistence of C. pneumoniae in mononuclear cells is poorly understood. To study the morphology and biological characteristics of the infection, human peripheral blood monocytes were infected with C. pneumoniae. Freshly isolated monocytes resisted the development of infectious progeny, and confocal and transmission electron microscopy showed that the morphology of the inclusions and chlamydial particles was abnormal. Addition of tryptophan or antibodies against gamma interferon did not diminish the inhibition of C. pneumoniae, suggesting that other factors are involved in the chlamydiostatic activity of the monocytes. Chlamydial mRNA was expressed at least 3 days after infection, however, and a capability for infected monocytes to induce a positive lymphocyte proliferative response was detected for up to 7 days, indicating that C. pneumoniae remains metabolically active in the monocytes in vitro. These results are in accordance with the hypothesis that C. pneumoniae may participate in the maintenance of local immunological response and inflammation via infected monocytes and thus enhance atherosclerosis.

Demonstration of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms.

BACKGROUND: Seroepidemiologic studies have indicated an association between chronic Chlamydia pneumoniae infection and coronary heart disease. The organism, which is a common respiratory pathogen, has been demonstrated in atherosclerotic lesions of the aorta and coronary arteries. Abdominal aortic aneurysms are frequently associated with atherosclerosis, and inflammation may actually be an important factor in aneurysmal dilatation. Hence it could be assumed that C. pneumoniae may play a role in maintaining an inflammation and triggering the development of aortic aneurysms. METHODS AND RESULTS: Specimens from abdominal aortic aneurysm were examined for the presence of C. pneumoniae by immunohistochemical analysis, the polymerase chain reaction amplifying omp 1 gene, transmission electron microscopy, and culture methods with histologically atherosclerosis-negative human aortic tissues used as a control group. Chlamydial lipopolysaccharide and C. pneumoniae specific antigens were found by immunohistochemistry in 12 and 8 of 12 aneurysm specimens, respectively, and C. pneumoniae DNA could be demonstrated in 6 of 6 aneurysm specimens studied. Furthermore electron microscopy revealed the presence of Chlamydia-like elementary bodies in three of four aneurysm specimens tested. None of the control samples gave positive reaction in the polymerase chain reaction, and C. pneumoniae antigens were not detected in any of them. CONCLUSIONS: C. pneumoniae is frequently found in the vessel wall of abdominal aortic aneurysm. The potential etiopathogenetic role of C. pneumoniae in the development of these aneurysms remains to be studied.