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Previous issue date: 2018-04-27 / Bj-PRO-7a, a proline-rich oligopeptide isolated from Bothrops jararaca snake
venom, was able to reduce blood pressure and heart rate in hypertensive
animals. However, it is not yet known whether this peptide may have beneficial
effects on cardiac remodeling. Herein, we evaluate the effect of the Bj-PRO-7a
in spontaneously hypertensive rats. Normotensive (Wistar) and spontaneously
hypertensive (SHR) rats were divided into 3 groups: 1) Wistar treated with 0.9%
saline, s.c.; 2) SHR treated with 0.9% saline, s.c.; and 3) SHR treated with BjPRO-7a
(71 nmol/Kg/day, s.c.). The animals were treated during 28 days. The
systolic blood pressure was weekly measured by tail-cuff plethysmography. At
the end of the treatment, cardiac function was evaluated in isolated perfused
heart preparation. The ventricular mass index was calculated by the ratio
between the left ventricular weight and tibia length. The cardiomyocyte diameter
and interstitial and perivascular fibrosis of the left ventricle were evaluated using
the Picrossirius staining. The detection of collagen III deposition was evaluated
by immunofluorescence. Fibroblast proliferation were assessed by
immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). The
expression of catalase, SOD and ERK1/2, MMP-2 and MMP-9 was assessed
by Western Blot. In our protocol, the Bj-PRO-7a was unable to reduce the
systolic blood pressure of the SHRs. However, this peptide attenuated the
development of the cardiomyocyte hypertrophy in these animals. Additionally,
the deposition of the interstitial and perivascular fibrosis in SHR was
significantly reduced by the treatment with Bj-PRO-7a. This peptide did not alter
the collagen III deposition in hypertensive rat hearts. The Bj-PRO-7a reduced
positive PCNA-labeled fibroblasts. The expression of catalase, SOD and
ERK1/2 was significantly increased in SHR, but the Bj-PRO-7a attenuates this
increase. The expression of MMP-2 and MMP-9 was not different in SHR
hearts, but the Bj-PRO-7a increased the expression of the MMP-2 in the heart
of these animals. Our findings demonstrate that the Bj-PRO-7a reduced the
pathological cardiac remodeling through mechanism mediated by inhibition of
the ERK1/2 and increasing MMP-2 expression. This data suggest that the Bj-
xxiii
PRO-7a could have a potential therapeutic for the treatment of cardiac
diseases. / O Bj-PRO-7a é um heptapetídeo pertencente à família de oligopeptídeo rico em
prolina isolado do veneno da serpente Bothrops jararaca. Estudos in vivo,
mostraram que a administração aguda do heptaptídeo é capaz de reduzir a
pressão arterial e a frequência cardíaca de animais hipertensos. Ainda pouco
estudado e considerando os efeitos antihipertensivo e bradicardico, avaliamos
o remodelamento cardíaco de animais hipertensos tratados com o Bj-PRO-7a.
No presente estudo, foram utilizados ratos normotensos (Wistar) e
espontaneamente hipertensos (SHR) que foram separados em 3 grupos
experimentais e receberam: 1) Wistar, 0,9% NaCl, (150 µl/dia, s.c.); 2) SHR,
0,9% NaCl, (150 µl/dia, s.c.); e 3) SHR tratado com Bj-PRO-7a (71 nmol/Kg/dia,
s.c.). As injeções (in bolus) foram repetidas diariamente durante 28 dias.
Durante o tratamento, os animais tiveram a pressão arterial sistólica (PAS)
mensurada semanalmente, pelo método não invasivo de plestimografia. No
final do tratamento, a função cardíaca foi avaliada pelo método de Langendorff.
A hipertrofia cardíaca de SHRs foi avaliada com análise dos seguintes
parâmetros: índice de massa ventricular, diâmetro do cardiomiócito, fibrose
intersticial e perivascular, colágeno III, proliferação de fibroblastos e expressão
da catalase, SOD, ERK1/2, MMP-2 e MMP-9. Nossos resultados mostram que
o tratamento crônico com Bj-PRO-7a não promoveu alterações importantes na
PAS de SHRs. No entanto, este peptídeo atenuou o desenvolvimento da
hipertrofia dos cardiomiócitos de SHRs. Apesar do Bj-PRO-7a não ter alterado
a deposição de colágeno III, foi capaz de reduzir a deposição de colágeno
intersticial e perivascular, bem como, a proliferação de fibroblastos em SHR. A
linhagem de ratos hipertensos, tem expressão de CAT, SOD e ERK1/2
significativamente maior do que em ratos normotensos. O Bj-PRO-7a atenuou
o aumento da expressão dessas enzimas / proteínas. Por outro lado, aumentou
a expressão da MMP-2 ativa nos corações de ratos hipertensos. Nossos
resultados mostram que o Bj-PRO-7a reduziu o remodelamento cardíaco
patológico através de mecanismos mediados pela inibição da ERK1/2 e
aumento da expressão da MMP-2. Dessa forma, os resultados sugerem que o
Bj-PRO-7a apresenta um potencial terapêutico para desenvolvimento de
fármacos para o tratamento de doenças cardiovasculares.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.bc.ufg.br:tede/8676 |
| Date | 27 April 2018 |
| Creators | Jesus, Érika Fernandes de |
| Contributors | Castro, Carlos Henrique de, Ianzer, Danielle Alves, Castro, Carlos Henrique de, Ianzer, Danielle Alves, Ferreira, Anderson José, Biancardi, Manoel Francisco |
| Publisher | Universidade Federal de Goiás, Programa de Pós-graduação em Biologia (ICB), UFG, Brasil, Instituto de Ciências Biológicas - ICB (RG) |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFG, instname:Universidade Federal de Goiás, instacron:UFG |
| Rights | http://creativecommons.org/licenses/by-nc-nd/4.0/, info:eu-repo/semantics/openAccess |
| Relation | 6883982777473437920, 600, 600, 600, -3872772117827373404, 7737708247419018223 |
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