• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2020.tde-31102020-191403
Document
Author
Full name
Julliana Carvalho Campos de Oliveira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Higuchi, Maria de Lourdes (President)
Garavelo, Shérrira Menezes
Ramires, Jose Antonio Franchini
Soares, Paulo Rogério
Title in Portuguese
Interação do micoplasma e do SUMO na aterogênese e na resposta antilipemiante e anti-inflamatória do composto PTCTS em coelhos com dieta hipercolesterolêmica
Keywords in Portuguese
Aterosclerose
Infecção
Mycoplasma pneumoniae
PTCTS
Sumoilação
Transialidase
Abstract in Portuguese
Introdução: Aterosclerose não é classificada como uma doença infecciosa, mas há evidências crescentes de que o estresse oxidativo, a inflamação, o diabetes, a obesidade e doenças valvares podem ser desencadeados por agentes infecciosos. Trabalhos prévios do laboratório mostraram grande quantidade de agentes infecciosos, principalmente o Mycoplasma pneumoniae nas placas de aterosclerose. Essa bactéria pode modular negativamente o sistema de modificação pós traducional, SUMO, para aumentar sua proliferação e infecção, inativando o sistema imunológico. PTCTS, uma nova droga que transloca o ácido siálico, foi usado na forma aquosa e diminuiu micropartículas de antígenos de M.pneumoniae no soro, mas não o tamanho das placas em estudos anteriores. Objetivo: Avaliar se nova formulação do composto em gel tem eficácia na remoção do M.pneumoniae podendo reestabelecer o sistema imunológico através do SUMO e diminuir aterosclerose. Métodos: Coelhos alimentados com dieta rica em colesterol ou não por 12 semanas receberam ou não tratamento com PTCTS e foram divididos em 3 grupos de 9 animais: CPositivo com dieta e sem tratamento; PTCTS com dieta e tratamento e CNegativo sem dieta e tratamento. As Aortas foram estudadas pelas técnicas de Imunohistoquímica para SUMO1, SUMO2/3, oxLDL e macrófago, TUNEL, Hibridação in situ e PCR real time quantitativo para DNA de M. pneumoniae e Western blotting para NFkB e receptor de LDL. Resultados: A dieta hipercolesterolêmica aumentou a quantidade de colesterol total (p=0,0003) nos grupos ateroscleróticos. O PTCTS diminuiu a porcentagem de área com placas de ateroma (p=0,015), do DNA de M. pneumoniae na placa na porção abdominal (p=0,02) e de oxLDL nas porções ascendente e abdominal (p=0,02 e 0,01, respectivamente) e aumentou na porção abdominal a quantidade de SUMO1 (p=0,04), SUMO2/3 (p=0,03), de células apoptóticas (p=0,005) e de NFkB (p=0,01). Conclusão: PTCTS em gel mostrou melhor eficiência na remoção do M. pneumoniae promovendo uma ação antiaterosclerótica, anti-inflamatória e antilipemiante; aumentou proteínas sumoiladas e NFkB melhorando a resposta imune, reduzindo todos os elementos pesquisados que contribuem para a progressão da aterosclerose
Title in English
Interaction between mycoplasma and SUMO in atherogenesis and the anti-lipid and anti-inflammatory response of the PTCTS compound in rabbits on a hypercholesterolemic diet
Keywords in English
Atherosclerosis
Infectious disease
Mycoplasma pneumoniae
Nanoparticles
Sumoylation
Transialidase
Abstract in English
Introduction: Atherosclerosis is not classified as an infectious disease, but there are many evidences that oxidative stress, inflammation, diabetes obesity and valve diseases can be triggered by infectious agents. Previous laboratory works showed large amount of infectious agents in human atherosclerosis, mainly Mycoplasma pneumoniae. This bacterium can use the post-translational modification system, SUMO, to increase its proliferation and infection by inactivating the immune system. PTCTS is a drug containing nanoparticles that translocates sialic acid, preventing mycoplasma from entering the cell and can also trigger inflammatory processes and the progress of atheromatous plaque. Objective: To assess whether the new PTCTS formulation in gel compound is effective in removing M. pneumoniae and if it can re-establish the immune system through SUMO, reducing, atherosclerosis. Methods: This trial studied rabbits that were fed with a cholesterol-rich diet, or not, for 12 weeks and received, or not, treatment with PTCTS, being divided into 3 groups: CPositive with diet and without treatment; PTCTS with diet and treatment and CNegative without diet and treatment. The collected Aortas were used in the immunohistochemistry techniques for SUMO1, SUMO2 / 3, oxLDL and macrophage, Tunel, In situ hybridization and quantitative real time PCR for M. pneumoniae DNA and Western blotting for NFkB and LDL receptor. Results: The hypercholesterolemic diet increased the amount of total cholesterol (p=0.0003) in atherosclerotic groups. PTCTS decreased the amount of percentage of the area with atheromatous plaques (p=0.015), M. pneumoniae bacteria in the abdominal portion (p=0.02) and oxLDL in the ascending and abdominal portions (p=0.02 and 0.01, respectively) and increased the amount of SUMO1 (p=0.04), SUMO2 / 3 (p=0.03), apoptotic cells (p=0.005) and NFkB (p=0.01) in the abdominal portion. Conclusion: PTCTS has shown a better efficiency in the removal of the bacterium M. pneumoniae promoting an anti-atherosclerotic, anti-inflammatory and antilipemiant action, increasing sumoilated proteins and NFkB to improve the immune response, being able to reduce atherosclerosis in all aspects studying
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2021-01-19
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2024. All rights reserved.