Effects of sodium butyrate on endothelial dysfunction induced by lysophosphathidylcholine

Effects of sodium butyrate on endothelial dysfunction induced by lysophosphathidylcholine

• Autor
• Melissa Tainan Silva Dias
• Co-autores
• Edenil Costa Aguilar , Luciano dos Santos Agum Capettini , Weslley Fernandes Braga , Natália Fernanda do Couto , Luciana de Oliveira Andrade , Jacqueline Isaura Alvarez-Leite
• Resumo

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  Introduction: Lipids oxidation is a key risk factor for cardiovascular disease triggering endothelial dysfunction. Lysophosphatidylcholine (LPC), a major component in oxidized LDL, is an important agent in atherogenesis. Recently, it has been described that butyrate, a short-chain fatty acid, has atheroprotective effects. Objective: Evaluate the role of sodium butyrate in LPC-induced endothelial dysfunction. Materials and methods: The vascular response to phenylephrine (Phe) and to acetylcholine (Ach) was performed in aortic rings from male mice (C57BL/6J), incubated with butyrate (0.01 and 0.1 Mm) and LPC (10 µM), with or without TRIM (a nNOS inhibitor). In addition, endothelial cells (EA.hy296) were incubated with LPC and butyrate for 2 h, to evaluate nitric oxide and ROS production, calcium flux (by flow cytometry, using fluorescent probes), and the expression/activation of ERK ½ and MKP-1 (by western blot). Data are presented as mean±SEM and were analyzed by Shapiro–Wilk test, for continuous variables, and by two-way ANOVA followed by post hoc Tukey's test (p<0.05).  

  Results:  Butyrate (0.1 mM) prevented endothelial dysfunction induced by LPC (Relaxation %: CT: 98.55±1.60, LPC: 82.10±4.53, LPC+BUT0.01mM: 85.23±1.42, LPC+BUT0.1mM: 98.96±1.55; Contraction mN: CT: 2.03±1.23, LPC: 4.01±1.23, LPC+BUT0.01mM: 2.09±0.44, LPC+BUT0.1mM: 1.69±1.16). In endothelial cells, butyrate prevented the LPC-induced reduction of NO production (CT: 66.12±0.57, LPC:37.97±0.22, LPC+BUT0.01mM: 79.9±1.27, BUT0.1mM: 63.47±0.82), restored Ca2+ internal transit (Fluo4 CT: 1.07±0.04, LPC:1.69±0.15, LPC+BUT0.01mM: 1.48±0.13, LPC+BUT0.1: 1.01±0.03), and reduced the production of ROS (CT: 40.2±0.52, LPC: 69.13±5.73, LPC+BUT0.01mM: 39.72±0.55, LPC+BUT0.1mM: 46.57±0.56). In the presence of TRIM, the results suggest that these effects occur mainly via nNOS. We also observed decreased LPC-induced phosphorylation of ERK ½ (CT 0.37±0.09, LPC: 079±0.04, LPC+BUT0.01mM: 0.54±0.06, LPC+BUT0.1mM: 0.86±0.06), in a MKP-1 independent manner (CT: 0.72±0.04, LPC: 0.17±0.2, LPC+BUT0.01mM: 0.2±0.01, LPC+BUT0.1mM: 0.5±0.03).

  Conclusion: Sodium butyrate inhibited LPC-induced vascular dysfunction by increasing NO production, by reducing ERK ½ activation.

• Palavras-chave
• Endothelial dysfunction, lysophosphatidylcholine, sodium butyrate, nitric oxide and neuronal nitric oxide synthase.
• Área Temática
• Apresentações Orais - Sessão VII

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