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Bothrops jararaca peptide with anti-hypertensive action normalizes endothelium dysfunction involved in
Gabriel Benedetti1, Katia L P Morais, Juliano R Guerreiro
1Center for Applied Toxinology-Centros de Pesquisa, Inovacio e Difusao, Instituto Butantan, Sao Paulo, Brazil.
Insights
A novel peptide, Bj-PRO-10c, from snake venom shows promise for treating preeclampsia. It boosts nitric oxide (NO) production and normalizes endothelial function in cells from preeclamptic women.
Area of Science:
- Pharmacology
- Obstetrics
- Cardiovascular Research
Background:
- Preeclampsia is a serious pregnancy disorder causing maternal and fetal complications, particularly in developing nations.
- Existing treatments for preeclampsia are limited, highlighting the need for novel therapeutic strategies.
- Bj-PRO-10c, a peptide from Bothrops jararaca venom, exhibits anti-hypertensive properties, with prior studies linking its effects to nitric oxide (NO) production.
Purpose of the Study:
- To investigate the in vitro effects of Bj-PRO-10c on human umbilical vein endothelial cells (HUVEC) from women with preeclampsia (HUVEC-PE) and normotensive pregnant women (HUVEC).
- To determine if Bj-PRO-10c can restore normal nitric oxide (NO) production and endothelial function in HUVEC-PE.
- To explore the potential of Bj-PRO-10c as a therapeutic agent for preeclampsia.
Main Methods:
- In vitro study using HUVEC-PE and HUVEC.
- Measurement of NO production, endothelial nitric oxide synthase (eNOS) expression, and argininosuccinate synthase activity.
- Assessment of intracellular calcium fluxes and superoxide production.
Main Results:
- Bj-PRO-10c significantly increased NO production in HUVEC-PE to levels comparable to HUVEC.
- The peptide enhanced eNOS expression and argininosuccinate synthase activity in HUVEC-PE.
- Bj-PRO-10c inhibited excessive superoxide production and induced intracellular calcium fluxes in HUVEC-PE, leading to eNOS activation.
Conclusions:
- Bj-PRO-10c demonstrates therapeutic potential by restoring endothelial NO production and function in preeclampsia.
- The peptide's specific effects on HUVEC-PE suggest a targeted mechanism for treating preeclampsia.
- Bj-PRO-10c may represent a promising novel therapeutic candidate for managing preeclampsia.
Abstract:
Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, is a major cause of fetal and maternal morbidity and mortality especially in developing countries. Bj-PRO-10c, a proline-rich peptide isolated from Bothrops jararaca venom, has been attributed with potent anti-hypertensive effects. Recently, we have shown that Bj-PRO-10c-induced anti-hypertensive actions involved NO production in spontaneous hypertensive rats. Using in vitro studies we now show that Bj-PRO-10c was able to increase NO production in human umbilical vein endothelial cells from hypertensive pregnant women (HUVEC-PE) to levels observed in HUVEC of normotensive women. Moreover, in the presence of the peptide, eNOS expression as well as argininosuccinate synthase activity, the key rate-limiting enzyme of the citrulline-NO cycle, were enhanced. In addition, excessive superoxide production due to NO deficiency, one of the major deleterious effects of the disease, was inhibited by Bj-PRO-10c. Bj-PRO-10c induced intracellular calcium fluxes in both, HUVEC-PE and HUVEC, which, however, led to activation of eNOS expression only in HUVEC-PE. Since Bj-PRO-10c promoted biological effects in HUVEC from patients suffering from the disorder and not in normotensive pregnant women, we hypothesize that Bj-PRO-10c induces its anti-hypertensive effect in mothers with preeclampsia. Such properties may initiate the development of novel therapeutics for treating preeclampsia.
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