Carotenoids produced by yeast biomass protect mechanisms regulating endothelial barrier function from lipopolysaccharide-induced damage in the rat heart.

Expression of occludin and junctional adhesion molecule A (JAM-A), transmembrane proteins of tight junctions (TJs), was analysed to characterize endothelial paracellular permeability in the heart of rats subjected to a bolus of bacterial lipopolysaccharide (LPS) at a dose of 1 mg/kg. Potential protective effects of natural carotenoids (10 mg/kg/day) produced by yeast biomass Rhodosporidium kratochvilovae on expression of occludin and JAM-A also examined in LPS-injected rats (n = 6 per group). LPS decreased expression of occludin by 40% (P < 0.01), JAM-A by 36% (P < 0.001) and increased plasma levels of malondialdehyde (MDA) and lysosomal N-acetyl-b-D-glucosaminidase (NAGA) compared to controls. Ten-day diet rich in yeast biomass containing carotenoids (torularhodin, torulene, ß-carotene) attenuated LPS-induced changes in expression of TJ proteins as observed by increased expression of occludin by 30% (P < 0.05) and JAM-A by 61% (P < 0.001) to the control values. Carotenoids also reduced oxidative stress and cellular injury indicated by decreased levels of MDA and NAGA. The results show that diet rich in yeast biomass containing natural carotenoids could protect mechanisms regulating paracellular endothelial barrier function from LPS-induced damage in the heart.

Lipopolysaccharide-induced redistribution of myocardial connexin43 is associated with increased macrophage infiltration in both normotensive and spontaneously hypertensive rats.

We investigated whether changes in gap junction alpha-1 protein (Cx43) expression may be associated with macrophage-induced inflammation in the heart of spontaneously hypertensive rats (SHR). To examine mutual interactions of macrophage infiltration with Cx43 expression and redistribution, we applied a bolus of bacterial lipopolysaccharide (LPS) to SHR and age-matched normotensive Wistar rats. The results demonstrated association of Cx43 downregulation with increased infiltration of cardiac CD-68 macrophages and upregulation of nuclear factor-κB (NFκB) and tumor necrosis factor-α (TNF-α) expression in the heart of SHR. LPS application to SHR caused further degradation and redistribution of Cx43 accompanied with extensively increased macrophage infiltration and NFκB and TNF-α expression. LPS administration to Wistar rats resulted in elevation of cardiac CD-68 macrophages but it did not significantly affect total Cx43 expression. Our results are suggestive of regulation of Cx43 expression with macrophages-related inflammation in the heart of SHR. The data also indicate that SHR can be more sensitive to LPS than are normotensive rats.

Changes of microRNA-1, -15b and -21 levels in irradiated rat hearts after treatment with potentially radioprotective drugs.

The aim of this study was to measure expression levels of microRNAs (miRNAs) (miRNA-1, -15b and -21) in the rat myocardium after a single dose of ionizing radiation (6-7 Gy/min, total 25 Gy). The rats were treated with selected drugs (Atorvastatin, acetylsalicylic acid (ASA), Tadalafil, Enbrel) for six weeks after irradiation. MiRNAs levels were measured by RT-qPCR. Irradiation down-regulated miRNA-1 in irradiated hearts. In Tadalafil- and Atorvastatin-treated groups, miRNA-1 expression levels were further decreased compared with irradiated controls. However, Enbrel increased miRNA-1 level in irradiated hearts similarly to that in non-irradiated untreated group. Increase of miRNA-15b is pro-apoptotic in relationship with ischemia. Irradiation caused down-regulation of miRNA-15b. Administration of ASA in the irradiated group resulted in the increase of miRNA-15b expression compared to non-treated controls without irradiation. After Enbrel administration, miRNA-15b levels were overexpressed compared to non-treated normal group. MiRNA-21 belongs to the most markedly up-regulated miRNAs in response to cardiogenic stress. MiRNA-21 was increased nearly 2-fold compared to non-treated hearts whereas Tadalafil reduced miRNA-21 levels (about 40 %). Our study suggests that Enbrel and Tadalafil changed miRNAs expression values of the irradiated rats to the values of non-irradiated controls, thus they might be helpful in mitigation of radiation-induced toxicity.

Omega-3 fatty acids reduce lipopolysaccharide-induced abnormalities in expression of connexin-40 in aorta of hereditary hypertriglyceridemic rats.

Omega-3 fatty acids (omega3FA) are known to reduce hypertriglyceridemia- and inflammation-induced vascular wall diseases. However, mechanisms of their effects are not completely clear. We examined, whether 10-day omega3FA diet can reduce bacterial lipopolysaccharide-induced changes in expression of gap junction protein connexin40 (Cx40) in the aorta of hereditary hypertriglyceridemic (hHTG) rats. After administration of a single dose of lipopolysaccharide (LPS, 1 mg/kg, i.p.) to adult hHTG rats, animals were fed with omega3FA diet (30 mg/kg/day) for 10 days. LPS decreased Cx40 expression that was associated with reduced acetylcholine-induced relaxation of aorta. Omega3FA administration to LPS rats had partial anti-inflammatory effects, associated with increased Cx40 expression and improved endothelium dependent relaxation of the aorta. Our results suggest that 10-day omega3FA diet could protect endothelium-dependent relaxation of the aorta of hHTG rats against LPS-induced damage through the modulation of endothelial Cx40 expression.