A Fermented Whole Grain Prevents Lipopolysaccharides-Induced Dysfunction in Human Endothelial Progenitor Cells

Abstract

Endogenous and exogenous signals derived by the gut microbiota such as lipopolysaccharides (LPS) orchestrate inflammatory responses contributing to development of the endothelial dysfunction associated with atherosclerosis in obesity, metabolic syndrome, and diabetes. Endothelial progenitor cells (EPCs), bone marrow derived stem cells, promote recovery of damaged endothelium playing a pivotal role in cardiovascular repair. Since healthy nutrition improves EPCs functions, we evaluated the effect of a fermented grain, Lisosan G (LG), on early EPCs exposed to LPS. The potential protective effect of LG against LPS-induced alterations was evaluated as cell viability, adhesiveness, ROS production, gene expression, and NF-kB signaling pathway activation. Our results showed that LPS treatment did not affect EPCs viability and adhesiveness but induced endothelial alterations via activation of NF-kB signaling. LG protects EPCs from inflammation as well as from LPS-induced oxidative and endoplasmic reticulum (ER) stress reducing ROS levels, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defense. Moreover, LG pretreatment prevented NF-kB translocation from the cytoplasm into the nucleus caused by LPS exposure. In human EPCs, LPS increases ROS and upregulates proinflammatory tone, proapoptotic factors, and antioxidants. LG protects EPCs exposed to LPS reducing ROS, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defenses possibly by inhibiting NF-κB nuclear translocation.

Lisosan G Protects the Retina from Neurovascular Damage in Experimental Diabetic Retinopathy

“…In particular, LG treatment significantly reduces the increases in caspase-3 mRNA expression, active caspase-3 levels, and number of active caspase-3 immunolabeled cells provoked by OS or by diabetes. Antiapoptotic effects of LG have been documented in cultured human endothelial progenitor cells challenged with lipopolysaccharides [12]. Inhibition of retinal neuronal death results in ameliorated retinal function, as evaluated with ERG.…”

“…A molecular characterization of the components of LG has been provided previously [8], while a more specific analysis of the phenolic compounds contained in LG has been published recently [9]. Both in vitro and in vivo studies have shown that LG is highly effective in protecting and improving the bioactivity of different cell types, from hepatocytes to microvascular endothelial cells, through the control of both oxidative and inflammatory processes [6,7,8,9,10,11,12]. In particular, the positive effects of LG are likely to be associated with radical scavenging, attenuation of OS, strengthening of antioxidant defenses, and reduced nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) [6,12], which is an oxidant-sensitive transcription factor responsible for regulating gene expression of factors involved in inflammatory responses.…”

“…Both in vitro and in vivo studies have shown that LG is highly effective in protecting and improving the bioactivity of different cell types, from hepatocytes to microvascular endothelial cells, through the control of both oxidative and inflammatory processes [6,7,8,9,10,11,12]. In particular, the positive effects of LG are likely to be associated with radical scavenging, attenuation of OS, strengthening of antioxidant defenses, and reduced nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) [6,12], which is an oxidant-sensitive transcription factor responsible for regulating gene expression of factors involved in inflammatory responses. The antioxidant capacity of LG has been evaluated in vitro employing the oxygen radical absorbance capacity, the 2,2-diphenyl-1-picrylhydrazyl, and the cellular antioxidant activity tests/methods [9,13].…”

Maternal modifiers of the infant gut microbiota: metabolic consequences

“…Dietary changes can have major effects on microbial composition and release of LPS that provokes inflammation, insulin resistance, and may even program bone marrow-derived stem cells (Giusti et al 2017). The significant increase in common myeloid progenitor cells derived from the bone marrow in diet-induced obese mice is thought to be the result of an altered microbiota composition (Luo et al 2015).…”

Pyrroloquinoline quinone prevents developmental programming of microbial dysbiosis and macrophage polarization to attenuate liver fibrosis in offspring of obese mice

“…Evidence in rodents and nonhuman primates suggests that exposure to a high‐fat or Western‐style diet (WD; high fat, high sugar) during pregnancy and lactation creates a long‐lasting metabolic signature on the infant liver, its innate immune system, and microbiota, which together predispose the offspring to NAFLD and accelerate the transition of NAFLD to NASH . Dietary changes can have major effects on microbial composition and release of lipopolysaccharide (LPS), a key driver released by gram‐negative bacteria, that provoke inflammation, insulin resistance, and may even program bone marrow‐derived stem cells prior to the development of obesity. Inflammation in LPS‐exposed macrophages is causally linked through accumulation of mitochondrial reactive oxygen species and succinate secondary to metabolic reprogramming to a “Warburg” metabolism (increased aerobic glycolysis together with a reprogrammed tricarboxylic acid [TCA] cycle and decreased oxidative phosphorylation [OXPHOS]).…”