January 2003

Project leader: Professor PEKKA SAIKKU
Department of Medical Microbiology, University of Oulu, P.O.Box 5000, FIN-90014 University of Oulu, Finland, +358-8-5375900, pekka.saikku@oulu.fi

Doctoral students of the project:
Kari Poikonen, Dept. Medical Microbiology, University of Oulu, kari.poikonen@oulu.fi
Ying Yan, Dept. Medical Microbiology, University of Oulu, ying.yan@oulu.fi
Taina Korhonen, Dept. Medical Microbiology, University of Oulu, takorhon@mail.student.oulu.fi
Pirkka Vikatmaa, Helsinki University Hospital, pirkka.vikatmaa@hus.fi

Other researchers of the project:
Maija Leinonen, National Public Health Institute, maija.leinonen@ktl.fi
Sylvi Silvennoinen-Kassinen, Dept. Medical Microbiology, University of Helsinki, sylvi.silvennoinen-kassinen@oulu.fi
Mauri Lepäntalo, Helsinki University Hospital, mauri.lepantalo@hus.fi
Tuija Ikonen, Tampere University Hospital, tuija.ikonen@helsinki.fi

Key words: atherosclerosis, inflammation, Chlamydia pneumoniae, pathogen burden, genetic susceptibility

Abstract
During past decade, numerous studies have addressed the possible role of infectious agents in the pathogenesis of coronary heart disease (CHD) and atherosclerosis. Among bacteria, Chlamydia pneumoniae(Cpn) has been found to be most strongly associated with cardiovascular diseases (CVD). Herpes group viruses, notably cytomegalovirus (CMV), have been associated with atherosclerosis and restenosis. The new concept of pathogen burden as a risk factor for CHD has been introduced: individuals infected with multiple pathogens have high CRP levels as a marker of inflammation and the greatest relative risk for CHD. Thus, pathogens might contribute to the CHD by promoting inflammatory response, and microbes and inflammation might hence together contribute to the pathogenesis of atherosclerosis. There are several pathogenetic mechanisms by which microbes could directly or indirectly induce atherogenesis. Atherosclerosis is considered as an inflammatory disease and infections induce host inflammatory response. Genetic background may predispose the host to susceptibility to chronic infection and predetermine the outcome of infection. Because inflammation plays a key role in atherosclerosis, the genes encoding inflammatory markers and the genetic variants regulating their expression are potential risk factors for atherosclerosis.

The goal of our study is to study the etiological role of Cpn, CMV and several other microbes (infection burden) and the host inflammatory response using specimens obtained from the patients with atherosclerotic diseases. The carotid and aortic samples will be collected from patients who are operated for carotid stenosis, abdominal aortic aneurysm or aortic occlusive disease. The microbes in the lesion are sought for by several methods. The expression of genes associated to immune response, cell activation, inflammation and growth factors is studied. The presence of different microbes is correlated to markers of cell activation and inflammation. The effect of individual genetic background is studied by determining polymorphism of several genes associated to inflammation and lipid metabolism.

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