Research Grants 14/04383-4 - Cardiopatias, Valva mitral - BV FAPESP
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Biomolecular products study of Chlamydia pneumoniae, Mycoplasma pneumoniae and Borrelia burgerdorferi in the pathogenesis of myxomatous mitral valve

Abstract

The myxomatous mitral valve disease compromises the valve by an imbalance in the amount of acid mucopolysaccharides array being clinically expressed by mitral valve prolapse (MVP). The etiology is still not fully understood and may occur in familial forms with autosomal dominant transmission that can be time-dependent or environmental factors likely. The prevalence in the general population has levels ranging from 2.5% to 30%. The typical myxomatous valve presents itself on macroscopic as a loose structure, with thickened and redundant leaflets, with increased total area and look for shells or dome. The pathogenesis of degenerative valve disease is still very controversial issue, and the chances of autoimmunity and the genetic alteration most frequently rose. Participation of collagenase has been suggested. As in atherosclerosis where classically associated factors such as cholesterol cannot explain the existing inflammation, and infectious agents (Chlamydia pneumonia-PC and Mycoplasma pneumonia-PM) have been found in large quantities in vulnerable atherosclerotic plaques and also related genetic polymorphisms, these factors could be participating in this inflammation in valvular heart disease.Besides the factors classically associated with atherosclerosis, infectious agents (PC and PM) found in large quantities in vulnerable atherosclerotic plaquet, could be participating in this inflammation in valvular heart disease. Higuchi et al., in a study that showed the involvement of microorganisms in the development of chronic inflammatory diseases, degenerative and consumptive, in humans and animals, made a comparison between multiple valve disease (stenosis or insufficiency due to rheumatic disease, calcified aortic stenosis and prolapse mitral valve). This work was a general approach on the presence of infectious agents in these valves and the possible pathogenetic involvement of those who had never even been investigated, focusing mainly PC and PM. We also found in a previous study a high incidence of antigens and forms of Borrelia burgerdorferi (BB) in electron microscopy. In this project, we focus on these three bacterial agents in mitral valve prolapse and evaluate on a possible role of these agents in symbiosis or not, in the pathogenesis of myxomatous mitral valve. Furthermore, genes archaea have been described in persistent pathogens apparently they confer metabolic capacity as an adaptive strategy for survival in hostile environments. Microparticles similar to archaea have been described in vulnerable atheromatous plaques in association with myxoid matrix. In unpublished study also verified the association of these microparticles with collagenase MMP9 and archaea collagenase AMZ1, who was also raised in patients with Chagas' disease with heart failure. Thus, we intend to relate the presence of antigens from infectious agents, inflammatory response and with collagenase (MMP9 and AMZ1) in the areas of myxoid degeneration compared with more fibrotic areas of the mitral valve.The study will examine two groups of 20 fragments in each group: Group I, composed of fragments of mitral valve tissue with clinical diagnosis of myxomatous extracted in replacement or mitral valvuloplasty group II, formed by segments of mitral valves without clinical disease. The analysis techniques are: 1)Staining with hematoxylin and eosin (H&E) and Movat. In H&E analysis will be made of the amount of fibrosis, calcification and areas of mucoid degeneration. In Movat, we evaluate the presence of tissue compromised by myxoid degeneration. 2)Immunohistochemistry to detect antigens of BB, PC, PM, inflammatory mediators (CD20 CD45 CD68) and markers collagen (MMP9 AMZ1). 3)Quantitative analysis of microscopic features is performed with image analyzer Aperio Image Scope View software to detect the percentage of positive area occupied by the respective antigens. 4)Transmission electron microscopy for direct visualization of PC, PM and BB. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TIVERON, MARCOS GRADIM; ALBERTO POMERANTZEFF, PABLO MARIA; HIGUCHI, MARIA DE LOURDES; REIS, MARCIA MARTINS; PEREIRA, JAQUELINE DE JESUS; KAWAKAMI, JOYCE TIEKO; IKEGAMI, RENATA NISHIYAMA; DE ALMEIDA BRANDAO, CARLOS MANUEL; JATENE, FABIO BISCEGLI. Infectious agents is a risk factor for myxomatous mitral valve degeneration: A case control study. BMC INFECTIOUS DISEASES, v. 17, . (14/04383-4)

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