Universidade Federal de Minas Gerais

About: Universidade Federal de Minas Gerais is a education organization based out in Belo Horizonte, Minas Gerais, Brazil. It is known for research contribution in the topics: Population & Context (language use). The organization has 41631 authors who have published 75688 publications receiving 1249905 citations.

Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation

Abstract: Background & aims Butyrate is a four-carbon fatty acid that presents anti-inflammatory, anti-oxidative and apoptotic properties in colon and several cell lines. Because atherosclerosis has important oxidative and inflammatory components, butyrate could reduce oxidation and inflammation, impairing atherogenesis. We evaluated the effects of butyrate supplementation of butyrate on atherosclerosis and its mechanisms of action. Methods and results ApoE knockout mice were fed on chow diet or 1% butyrate-supplemented chow diet (Butyrate) for 10 weeks to assess atherosclerosis lesions area and inflammatory status. Macrophage and endothelial cells were also pretreated with butyrate (0.5 mM) for 2 h before oxLDL stimulation to study oxLDL uptake and pro and anti-inflammatory cytokine production. Butyrate reduced atherosclerosis in the aorta by 50%. In the aortic valve, butyrate reduced CCL2, VCAM1 and MMP2 productions in the lesion site, resulting in a lower migration of macrophage and increased collagen depositions in the lesion and plaque stability. When EA.hy926 cells were pretreated with butyrate, oxLDL uptake, CD36, VCAM1, CCL2 TNF, IL1β and IL6 productions were reduced, whereas IL10 production was increased. These effects were accompanied by a lower activation of NFκB due to a lower nuclear translocation of the p65 subunit. Conclusion Oral butyrate is able to slow the progression of atherosclerosis by reducing adhesion and migration of macrophages and increasing plaque stability. These actions are linked to the reduction of CD36 in macrophages and endothelial cells, decreased pro-inflammatory cytokines and lower activation of NFκB all of these data support a possible role for butyrate as an atheroprotective agent.

Nonpeptide AVE 0991 Is an Angiotensin-(1–7) Receptor Mas Agonist in the Mouse Kidney

Abstract: It has been described recently that the nonpeptide AVE 0991 (AVE) mimics the effects of angiotensin-(1-7) [Ang-(1-7)] in bovine endothelial cells. In this study, we tested the possibility that AVE is an agonist of the Ang-(1-7) receptor Mas, in vitro and in vivo. In water-loaded C57BL/6 mice, AVE (0.58 nmol/g body weight) produced a significant reduction in urinary volume (0.06±0.03 mL/60 min [n=9] versus 0.27±0.05 [n=9]; P<0.01), associated with an increase in urinary osmolality. The Ang-(1-7) antagonist A-779 completely blocked the antidiuretic effect of AVE. As observed previously for Ang-(1-7), the antidiuretic effect of AVE after water load was blunted in Mas-knockout mice (0.37±0.10 mL/60 min [n=9] versus 0.27±0.03 mL/60 min [n=11] AVE-treated mice). In vitro receptor autoradiography in C57BL/6 mice showed that the specific binding of 125I-Ang-(1-7) to mouse kidney slices was displaced by AVE, whereas no effects were observed in the binding of 125I-angiotensin II or 125I-angiotensin IV. Furthermore, AVE displaced the binding of 125I-Ang-(1-7) in Mas-transfected monkey kidney cells (COS) cells (IC50=4. 75×10-8 mol/L) and of rhodamine-Ang-(1-7) in Mas-transfected Chinese hamster ovary (CHO) cells. It also produced NO release in Mas-transfected CHO cells blocked by A-779 but not by angiotensin II type-1 (AT1) and AT2 antagonists. Contrasting with these data, the antidiuretic effect of AVE was totally blocked by AT2 antagonists and partially blocked (≈60%) by AT1 antagonists. The binding data, the results obtained in Mas-knockout mice and in Mas-transfected cells, show that AVE is a Mas receptor agonist. Our data also suggest the involvement of AT2/AT1-related mechanisms, including functional antagonism, oligomerization or cross-talk, in the renal responses to AVE.