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Master's Dissertation
DOI
10.11606/D.17.2008.tde-18112010-110823
Document
Author
Full name
Karina Magalhães Alves da Mata
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2008
Supervisor
Committee
Ramos, Simone Gusmão (President)
Metze, Konradin
Rossi, Marcos Antonio
Title in Portuguese
Participação das Metaloproteinases 2 e 9 no desenvolvimento de aneurisma da aorta abdominal em ratos Wistar
Keywords in Portuguese
Aneurisma
estenose
fluxo turbulento
lesão vascular
MMP-2
MMP-9
remodelamento vascular
Abstract in Portuguese
A degradação da matriz extracelular e de proteínas da parede aórtica associada à inflamação é uma das principais características dos aneurismas da aorta abdominal (AAA). O objetivo deste trabalho foi investigar a participação das metaloproteinases 2 e 9 na formação de AAAs, através de um modelo experimental inédito de indução de AAA em ratos Wistar, desencadeado por duas potenciais causas de secreção e ativação de MMP-2 e 9: alteração do fluxo sanguíneo e lesão vascular externa na aorta. A formação de aneurismas foi observada em 60%-70% dos animais, apresentando diâmetro de 7 a 8 vezes maior que o diâmetro normal da aorta. Histologicamente observou-se remodelamento, intensa resposta inflamatória, destruição maciça de fibras elásticas e aumento da síntese de colágeno na parede aórtica. A expressão de ambas as formas de MMP-2 foram observadas tanto nos AAAs como nos grupos controles, neste com menor atividade, entretanto a expressão da pró e da MMP-9 ativa foram encontradas apenas nos AAAs. Conclusão: Nossos resultados sugerem que tanto as MMP-2 quanto as MMP-9 apresentam importante papel no desenvolvimento de AAA e este novo modelo de indução de AAA, pode ajudar a elucidar os mecanismos que desencadeiam a secreção e ativação das MMP-2 e MMP-9 na formação de aneurismas.
Title in English
Participation of Metalloproteinases 2 and 9 in Developed of Aortic Abdominal Aneurysms in Wistar Rats.
Keywords in English
Aneurysm
injury
MMP-2
MMP-9
stenosis
turbulent flow
vascular remodeling
Abstract in English
Degradation of extracellular matrix and proteins associated with inflammation of the aortic wall is the main characteristics of the abdominal aortic aneurysms (AAA). The aim of this study was investigate the participation of Metalloproteinase 2 and 9 in AAA formation in Wistar rats. A novel experimental model of AAA was developed, providing two potential causes of MMPs secretion and activation, turbulent flow (caused by surgically induced extrinsic stenosis) and outside vascular injury is detailed described. The days analyzed were the 3rd and the 7th post surgery. Aneurysms were observed to occur in 60-70% of the Group AAA, exhibiting a major transversal diameter to 7 from 8 times larger than controls and sham groups. Histologically, the aneurysms wall showed extensive structural remodeling, intense inflammatory response, massive elastic fibers destruction and abundant collagen deposition. Increased pro- and active MMP-2 was demonstrated in the AAA and controls groups, whereas pro- and active MMP-9 were found to be expressed only in the AAA group. Conclusions: MMP-2 and MMP-9 may have a pivotal role in the development of experimental AAA. This model can help to elucidate the mechanisms which trigger off MMP-2 and MMP-9 secretion and activation causing aneurysms.
 
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Publishing Date
2010-12-14
 
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