Angiotensinogênio e receptores de angiotensina II, AT1 e AT2, em modelo porcino de cicatrização hipertrófica
Arquivos
Data
2009
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A cicatrização hipertrófica resulta de um complexo
conjunto de interações entre as células do sangue e da pele, intermediada
por moléculas pró e anti-inflamatórias, citoquinas, fatores de crescimento,
hormônios e vitaminas. Dentre estas moléculas, o sistema angiotensina,
relacionado em processos fibróticos de vários outros órgãos, parece ter
participação na fisiopatologia da cicatrização hipertrófica. Objetivo:
Avaliar a presença de moléculas constituintes do sistema angiotensina -
angiotensinogênio e receptores tipo I (AT1) e tipo II (AT2) da angiotensina
II - em porcas Duroc e Yorkshire. Métodos: Foram criadas cinco feridas
rasas e cinco feridas profundas no dorso de três porcas Duroc (grupo em
estudo que apresenta cicatrizes fibroproliferativas) e três porcas Yorkshire
(grupo controle com cicatrização não proliferativa). As feridas foram
biopsiadas após 1, 2, 3, 12 e 20 semanas e foi realizada imunohistoquímica
e qRT-PCR. A expressão destes genes nas feridas profundas
foi normalizada pela expressão das feridas rasas, a fim de se evidenciar os
genes diferentemente expressos na cicatrização hipertrófica quando
comparada a cicatrização normal. Resultados:Observou-se a coloração
positiva de receptores AT1 e AT2 na epiderme, derme, anexos e capilares
no decorrer do tempo. A expressão relativa de AT2 estava
significativamente hiperexpressa nas porcas Yorkshire duas e três semanas
após a criação das feridas. Não houve diferença de expressão de AGTN ou
AT1 neste modelo animal. Conclusão: AT1 e AT2 estão expressos nas
células constituintes da pele neste modelo de cicatrização hipertrófica. A
hiperexpressão de AT2 no grupo controle (Yorkshire) poderia ser
interpretada como uma das possíveis causas para a não formação de
cicatrizes fibroproliferativas nestes animais.
Introduction: Hypertrophic scar is a result of a complex interaction between blood and skin cells that is mediated by anti and pro inflammatory molecules, cytokines, growth factors, hormones and vitamins. It seems that angiotensin system, related to fibrosis in other organs, is one group of molecules related to hypertrophic scar pathophisiology. Purpose: To determine participation of angiotensin system and some of its molecules – angiotensinogen (AGTN), angiotensin II receptor type 1 (AT1) and type II (AT2) – in animal model of hypertrophic scarring. Methods: Five shallow and five deep wounds were created on the back of three Duroc (study group with fibroproliferative scars) and three Yorkshire pigs (control group with nonproliferative scars) Wounds were biopsied at 1, 2, 3, 12 e 20 weeks and immunohistochemistry and qRT-PCR were performed. Gene expression of AGTN, AT1 and AT2 in deep wounds were normalized to shallow wounds, to put in evidenced differentially expressed genes in hypertrophic scar when compared to normal healing. Results: Epidermis, dermis, skin appendages and capillary vessels were positive stained for AT1 and AT2 during time. Relative expression of AT2 was significantly overexpressed at 2 and 3 week after wounds creation Yorkshire pigs. There was not significant different expression for AGTN or AT1 in this animal model during time. Conclusion: AT1 and AT2 are expressed in skin cells in this hypertrophic scar animal model. Overexpression of AT2 in Yorkshire pigs could be interpreted as a possible cause of nonfibroproliferative scar formation in these pigs.
Introduction: Hypertrophic scar is a result of a complex interaction between blood and skin cells that is mediated by anti and pro inflammatory molecules, cytokines, growth factors, hormones and vitamins. It seems that angiotensin system, related to fibrosis in other organs, is one group of molecules related to hypertrophic scar pathophisiology. Purpose: To determine participation of angiotensin system and some of its molecules – angiotensinogen (AGTN), angiotensin II receptor type 1 (AT1) and type II (AT2) – in animal model of hypertrophic scarring. Methods: Five shallow and five deep wounds were created on the back of three Duroc (study group with fibroproliferative scars) and three Yorkshire pigs (control group with nonproliferative scars) Wounds were biopsied at 1, 2, 3, 12 e 20 weeks and immunohistochemistry and qRT-PCR were performed. Gene expression of AGTN, AT1 and AT2 in deep wounds were normalized to shallow wounds, to put in evidenced differentially expressed genes in hypertrophic scar when compared to normal healing. Results: Epidermis, dermis, skin appendages and capillary vessels were positive stained for AT1 and AT2 during time. Relative expression of AT2 was significantly overexpressed at 2 and 3 week after wounds creation Yorkshire pigs. There was not significant different expression for AGTN or AT1 in this animal model during time. Conclusion: AT1 and AT2 are expressed in skin cells in this hypertrophic scar animal model. Overexpression of AT2 in Yorkshire pigs could be interpreted as a possible cause of nonfibroproliferative scar formation in these pigs.
Descrição
Citação
RAMOS, Maria Luiza Christovão. Angiotensinogênio e receptores de angiotensina II, AT1 e AT2, em modelo porcino de cicatrização hipertrófica. 2009. 115f. Tese (Doutorado em Ciências) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2009.