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Presence of Chlamydophila pneumoniae DNA but not mRNA in stenotic aortic heart valves
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
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2010 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 143, no 1, 57-62 p.Article in journal (Refereed) Published
Abstract [en]

Background: The pathogenesis of aortic valve stenosis may involve inflammation and we have previously demonstrated Chlamydophila pneumoniae (C. pneumoniae) DNA in stenotic aortic heart valves. Dissemination of these bacteria is probably mediated by alveolar macrophages. Bacterial DNA alone does not indicate whether the bacteria are viable and replicating. This study aimed to investigate the presence of C. pneumoniae mRNA, a marker of replicating bacteria, and C. pneumoniae DNA in stenotic aortic valves and the prevalence of C. pneumoniae in peripheral blood mononuclear cells (PBMC).

Methods: DNA was extracted from heart valves and PBMC and mRNA from heart valves from 76 patients undergoing aortic valve replacement surgery. C. pneumoniae DNA and mRNA were measured by real-time PCR targeting the ompA gene.

Results: C. pneumoniae DNA was demonstrated in 22% of heart valves and in 5% of PBMC. C. pneumoniae mRNA was not detected in any valve. Patients positive for C. pneumoniae in the valve underwent coronary artery by-pass grafting more often (p = 0.01) and suffered from angina pectoris (p = 0.02) and arterial hypertension (p = 0.03) more often than patients negative for C. pneumoniae in the valve.

Conclusions: These findings support a role for C. pneumoniae in the pathogenesis of aortic valve stenosis and indicate that the bacteria disseminate from the respiratory tract long before the patients were in need of surgery and that the valve infection thereafter entered into a persistent and non-replicative state. Moreover, patients positive for C. pneumoniae in the valve more often needed by-pass grafting because of more advanced coronary disease.

Place, publisher, year, edition, pages
2010. Vol. 143, no 1, 57-62 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97117DOI: 10.1016/j.ijcard.2009.01.052ISI: 000280010700010OAI: oai:DiVA.org:uu-97117DiVA: diva2:171915
Available from: 2008-04-25 Created: 2008-04-25 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Chlamydophila pneumoniae in Cardiovascular Diseases: Clinical and Experimental Studies
Open this publication in new window or tab >>Chlamydophila pneumoniae in Cardiovascular Diseases: Clinical and Experimental Studies
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chlamydophila pneumoniae (C. pneumoniae) has been suggested as a stimulator of chronic inflammation in atherosclerosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 50% of patients with stable angina pectoris or acute coronary syndrome undergoing coronary artery bypass grafting. C. pneumoniae mRNA, a marker of replicating bacteria, was demonstrated in 18% of the aortic biopsies.

Inflammation may have a role in the pathogenesis of thoracic aortic aneurysm, aortic dissection and aortic valve stenosis. C. pneumoniae DNA was demonstrated in aortic biopsies in 26% of thoracic aortic aneurysm patients and in 11% of aortic dissection patients undergoing thoracic surgery and in 22% of stenotic aortic heart valves from patients undergoing aortic valve replacement. No bacterial mRNA was demonstrated in these aortic biopsies, nor in the valves, suggesting that the infection has passed into a persistent state. C. pneumoniae DNA was demonstrated in peripheral blood mononuclear cells in only 5% of aortic valve stenosis patients and not in thoracic aortic aneurysm or aortic dissection patients, suggesting that the bacterium disseminated to the cardiovascular tissue long before the patient required surgery. The copper/zinc ratio in serum, a marker of infection/inflammation, was significantly elevated in thoracic aortic aneurysm patients, supporting an inflammatory pathogenesis. Patients positive for C. pneumoniae in the aortic valve had more advanced coronary atherosclerosis, further supporting a possible role for C. pneumoniae in atherosclerosis.

Mice were infected with C. pneumoniae that disseminated to all organs investigated (i.e. lungs, heart, aorta, liver and spleen). Trace element concentrations were altered in infected animals with an increased copper/zinc ratio in serum, a progressively increased iron concentration in the liver and a progressively decreased iron concentration in serum. Iron is important for C. pneumoniae metabolism, and a changed iron homeostasis was noted in infected mice by alterations in iron-regulating proteins, such as DMT1 and hepcidin.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 340
Keyword
Communicable diseases, Chlamydophila pneumoniae, Chlamydia pneumoniae, trace elements, atherosclerosis, aortic valve stenosis, thoracic aortic aneurysm, aortic dissection, hepcidin, iron, Infektionssjukdomar
Identifiers
urn:nbn:se:uu:diva-8667 (URN)978-91-554-7176-7 (ISBN)
Public defence
2008-05-23, Hörsalen, Akademiska sjukhuset, ing. D1, Dag Hammarsköldsväg 17, Uppsala, 09:15
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Available from: 2008-04-25 Created: 2008-04-25Bibliographically approved

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