Efeito do peptídeo Bj-PRO-7a no remodelamento cardíaco em ratos hipertensos
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2018-04-27
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Universidade Federal de Goiás
Resumo
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-
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PRO-7a could have a potential therapeutic for the treatment of cardiac
diseases.
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JESUS, É. F. Efeito do peptídeo Bj-PRO-7a no remodelamento cardíaco em ratos hipertensos. 2018. 47 f. Dissertação (Mestrado em Biologia) - Universidade Federal de Goiás, Goiânia, 2018.