An Approach for Application of Synthetic Peptides as Markers of Atherosclerotic Diseases

Beata Kolesińska 1Michał Arabski 2Iwona Konieczna 2Dariusz Sołowiej 3Alicja Rogoń 4Wiesław Kaca 2Zbigniew J. Kamiński 1

1. Technical University of Łódź, Institute of Organic Chemistry (PŁ), Żeromskiego 116, Łódź 90-924, Poland
2. Department of Microbiology, Institue of Biology, Jan Kochanowski University, Świętokrzyska, Kielce 25-406, Poland
3. Gastroenterology Outpatient Clinic and Endoscopy Unit "Endomed", Zagórska, Kielce 25-355, Poland
4. Medical Laboratory "Diagnostyka", Jagielońska, Kielce 25-734, Poland

Abstract

Autoimmune or atherosclerotic diseases are resulted by multifunctional interactions including genetic predisposition, environmental circumstances, but also chronic bacterial or viral infections. One of essential factor is molecular mimicry of between human proteins and bacterial antigens observed in infections with P. mirabilis, H. pylori, Chlamydia and many others. In recent years, some papers have suggested that H. pylori plays a role in various extragastric diseases, for example, ischemic heart disease, idiopathic thrombocytopenic purpura, iron-deficiency anemia, and atherosclerosis. Since bacterial urease has been suggested to be a immunodominant antigen detected in infected persons, we considered that antibodies against this enzyme might be important in quest for the new marker of coronary heart diseases as well as Helicobacter-induced gastritis.

Peptide sequences (8-19-mer) characteristic for ureases of H. pylori, Proteus sp, Vibrio sp, Staphylococus, C. ensiformis were synthesized on solid phase using 2-chlorotrityl resin and triazine based coupling reagent (DMT/NMM/BF4) [1].

The study population consisted of 40 healthy blood donors and 30 atherosclerotic patients. We observed statistically significantly stronger reactions of BK-61A peptide with H. pylori-infected atherosclerotic patients than with H. pylori-infected healthy blood donors. One can suggest that H. pylori urease generated specific human antibodies which, by molecular mimicry reacted with native human tissue peptides. This may have started inflammatory processes, such as complement activation via the classical pathway and macrophage and neutrophil activation. Amino acid sequence similarity was analyzed by the Basic Local Alignment Search Tool (Blast), which showed that the H. pylori urease fragment SIKEDVQF demonstrates as much as 75% similarity to several human proteins.

[1] Michał Arabski, Iwona Konieczna, Dariusz Sołowiej, Alicja Rogoń, Beata Kolesińska,

Zbigniew J. Kamiński, Wiesław Kaca, Clinical Biochemistry, 43 (2010) 115–123.

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Presentation: Oral at VII Multidyscyplinarna Konferencja Nauki o Leku, by Zbigniew J. Kamiński
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-19 14:20
Revised:   2010-03-19 14:42
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