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university of tampere: faculty of medicine and life sciences: research: forensic medicine:
Faculty of Medicine and Life SciencesUniversity of TampereFaculty of Medicine and Life Sciences

Pathogenesis and genetics of sudden cardiac death and cardiovascular diseases

Rupture or erosion of a vulnerable plaque leads to coronary thrombosis causing unstable angina, acute myocardial infarction (MI), and most importantly sudden cardiac death (SCD). The triggering event for inflammation leading to plaque rupture has however remained unsolved. The involvement of bacteria in rupture of the atheroma has been speculated but never confirmed. The most commonly suspected infective agent has been considered to be Chlamydia pneumoniae or Porphyromonas gingivalis, but their role have been disputed due to failure in trials using long-term antibiotic treatment. Our study group was the first to show that autopsy coronary atheroma contained DNA of gram-positive viridans streptococci among other species of bacteria commonly found in oral cavity or gut. Recently, we reported that viridans streptococci were detected in 78.2% of thrombus aspirates of MI patients. However, there is still the possibility that sensitive molecular probes are picking up phagocytized bacterial DNA in macrophages or natural killer cells originating from non-cardiac site such as gingiva, skin, or respiratory tract; or that bacteria become attached as a biofilm to the uneven surface of the coronary plaque following bacteremia without any pathogenic or clinical significance.

In this study project comprising unique autopsy samples and clinical MI, stroke, aortic valve replacement patients as well as experimental smooth muscle cell cultures and knock-out mice, we applied sophisticated array of techniques including immunohistochemistry and gene expression assays to find out where these bacteria we have found in coronary plaques area alive or dead, where they come from, what is the bacterial diversity in the plaques, and how they end up in the atheroma.  We also aim to find out "normal" bacterial DNA level in blood and study whether positive blood qPCR bacteria results could be used to predict risk of MI. Genome wide analysis, metabolomics and lipidomics are used to reveal new pathways or markers to individually associate with coronary disease and interact with bacterial infection.  The present project can lead to a new concept of the pathogenesis of MI, to the discovery of new diagnostic tests, as well as new prevention and treatment perspectives.

The present study plan is a continuation of the 5- year project funded by European Union 7th Framework Program grant number 201668 for AtheroRemo Project, comprising 18 partners from 13 countries aiming to study the pathogenesis, genetics, diagnostics and treatment of vulnerable coronary plaque.

Mikkelsson J, Perola M, Penttilä A, Karhunen PJ. Platelet glycoprotein Ibalpha HPA-2 Met/VNTR B haplotype as a genetic predictor of myocardial infarction and sudden cardiac death. Circulation. 2001 Aug 21;104(8):876-80.

Norja S, Nuutila L, Karhunen PJ, Goebeler S. C-reactive protein in vulnerable coronary plaques. J Clin Pathol. 2007;60(5):545-8.

Karhunen V, Forss H, Goebeler S, Huhtala H, Ilveskoski E, Kajander O, Mikkelsson J, Penttilä A, Perola M, Ranta H, Meurman JH, Karhunen PJ. Radiographic assessment of dental  health in middle-aged men following sudden cardiac death.  J Dent Res. 2006 Jan;85(1):89-93.

Pessi T, Karhunen V, Karjalainen PP, Ylitalo A, Airaksinen JK, Niemi M, Pietila M, Lounatmaa K, Haapaniemi T, Lehtimäki T, Laaksonen R, Karhunen PJ, Mikkelsson J. Bacterial signatures in thrombus aspirates of patients with myocardial infarction. Circulation. 2013 Mar 19;127(11):1219-28

 
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Last update: 21.3.2014 13.49 Muokkaa

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