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Oxidized low-density lipoprotein (ox-LDL) accumulation is one of the critical determinants in endothelial dysfunction in many cardiovascular diseases such as atherosclerosis. C1q/TNF-related protein 9 (CTRP9) is identified to be an adipocytokine with cardioprotective properties. However, the potential roles of CTRP9 in endothelial function remain largely elusive. In the present study, the effects of CTRP9 on the proliferation, apoptosis, migration, angiogenesis, nitric oxide (NO) production and oxidative stress in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL were investigated. We observed that treatment with ox-LDL inhibited the proliferation, migration, angiogenesis and the generation of NO, while stimulated the apoptosis and reactive oxygen species (ROS) production in HUVECs. Incubation of HUVECs with CTRP9 rescued ox-LDL-induced endothelial injury. CTRP9 treatment reversed ox-LDL-evoked decreases in antioxidant enzymes including heme oxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase quinone 1, and glutamate-cysteine ligase (GCL), as well as endothelial nitric oxide synthase (eNOS). Furthermore, CTRP9 induced activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC1-α) and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Of interest, AMPK inhibition or PGC1-α silencing abolished CTRP9-mediated antioxidant enzymes levels, eNOS expressions, and endothelial protective effects. Collectively, we provided the first evidence that CTRP9 attenuated ox-LDL-induced endothelial injury by antioxidant enzyme inductions dependent on PGC-1α/AMPK activation. [ABSTRACT FROM AUTHOR]

Abstract Endothelial lesion response to injurious stimuli is a necessary step for initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from different marine sources is shown to exhibit anti-inflammatory properties. However, the potential roles and possible molecular mechanisms of Hy in endothelial inflammation have yet to be fully clarified. We showed that Hy significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro-inflammatory cytokines expressions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome proliferator-activated receptor γ (PPAR-γ) and upregulated toll-like receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4 expressions and decreases in PPAR-γ levels. Genetic silencing of TLR4 or PPAR-γ agonist pioglitazone obviously abrogated the levels of pro-inflammatory cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert anti-inflammatory actions through the regulation of TLR4 and PPAR-γ dependent on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent that can potentially relieve or ameliorate endothelial inflammation-associated diseases. [ABSTRACT FROM AUTHOR]

Background: Activation of macrophage is involved in many inflammation diseases. Lipopolysaccharide (LPS) is a powerful inflammatory signal contributing to monocytes/macrophages activation associated with increased proinflammatory cytokines expressions. We recently identified that vaccarin was expected to protect endothelial cells from injury. Hypaphorine was abundantly found in vaccaria semen. However, the potential roles and underlying mechanisms of vaccaria hypaphorine on macrophage inflammation have been poorly defined. Methods: This study was designed to determine the effects of vaccaria hypaphorine on LPS-mediated inflammation in RAW 264.7 cells. Results: In this study, we demonstrated that vaccaria hypaphorine dramatically ameliorated LPS-induced nitric oxide (NO) release and productions of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1) and prostaglandin E2 (PGE2) in RAW 264.7 cells. LPS-stimulated expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were down-regulated by vaccaria hypaphorine. Furthermore, vaccaria hypaphorine retarded LPS-induced phosphorylation of ERK, nuclear factor kappa beta (NFκB), NFκB inhibitor IκBα, and IKKβ. Immunofluorescence staining revealed that vaccaria hypaphorine eliminated the nuclear translocation of NFκB in LPS-treated RAW 264.7 cells. Conclusion: It was seen that vaccaria hypaphorine counteracted inflammation via inhibition of ERK or/and NF?B signaling pathways. Collectively, we concluded that vaccaria hypaphorine can be served as an anti-inflammatory candidate. [ABSTRACT FROM AUTHOR]

Endothelial cell injury is a critical component of atherosclerosis and hypertension. Vaccarin is considered to be of potential benefit in the treatment of vascular diseases. The aim of the present study was to evaluate the possible effects of vaccarin in human EA•hy926 cells induced by high glucose, and to investigate its underlying mechanism in the prevention and treatment of high glucose-induced injury. In the present study, EA•hy926 cells were exposed to 90, 180 and 270 mM high glucose for 24 h, and the induced cell injury was examined using a sulforhodamine B assay. Following treatment with high glucose, it was found that high glucose stimulated cell injury, resulting in reduced cell viability and migratory ability, increased lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity. High glucose further accelerated cell apoptosis via activating Notch1 and Hairy and enhancer of split 1. It was found that preincubation with vaccarin protected the EA•hy926 cells from high glucose-induced cell injury, which promoted cell viability and migratory ability, inhibited the expression levels of LDH and MDA, and enhanced the activity of SOD. Cell migratory ability, LDH leakage, MDA levels and decreasing SOD activity were evaluated using a wound healing assay and corresponding assay kits. Cell apoptosis was detected by flow cytometry with an Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and Hoechst staining. Furthermore, western blotting was used to detect the protein expression levels of Notch1, Hes1 and caspase-3. In particular, in addition to inducing the downregulation of Notch signaling, vaccarin treatment downregulated the cell apoptotic pathway-associated protein caspase 3. These findings suggested that vaccarin may be able to selectively protect the vascular endothelium from dysfunction induced by high glucose. [ABSTRACT FROM AUTHOR]

Reservoirs play an important role in modifying the natural hydrological regime. Reservoir-induced changes in flow fluctuations at monthly and hourly scales were analyzed through a case study of a tributary of the Yangtze River (China), the Qingyi River, where the Chencun reservoir is located at the upper reaches. Monthly and hourly flow data were collected from two flow gauging stations monitoring the inflow and outflow regimes, respectively. The flow fluctuations were characterized by coefficient of variation (CV) and concentration degree (Cd). Continuous Morlet wavelet transform was applied to detect diurnal period. The influence of the reservoir was revealed comparing the postdam with the predam conditions by and comparing the affected with the natural conditions. The results indicate two opposite change patterns. Reservoir impoundment may mitigate flow fluctuations at both of the monthly and the hourly scales. At a monthly scale, reservoirs usually impound water in the flood season for the dry season. At an hourly scale, reservoirs may restrain a flood pulse and strictly control the outflow. Thus, the reservoirs reduce variation and concentration of the runoff distribution within a year and within a day. In contrast, the reservoirs may aggravate the hourly flow fluctuation by releasing hydropeaking waves for hydropower generation and superimpose a diurnal period to the downstream flow regime. But the artificial diurnal fluctuation is of some uncertainty in terms of appearance time and duration. This work may deepen the understanding of the reservoirs influence mechanism on the downstream flow regime. [ABSTRACT FROM AUTHOR]

Angiogenesis is a major pathological component of several diseases, including traumatic vascular disease and coronary heart disease. The purpose of the present study was to determine the effects of vaccarin on endothelial cell migration and neovascularization, which are important and necessary components of wound healing. The present study investigated and confirmed neovascularization induced by vaccarin in vitro and in vivo. In vitro, the effects of vaccarin (1.08 and 2.15 µM) on proliferation, migration and tube formation of human microvascular endothelial cells (HMEC)-1 were evaluated via sulforhodamine B assay and migration and tube formation assay, respectively. Furthermore, a mouse Matrigel plus model was used to detect capillary-like tube structures in vivo. Immunohistochemistry was used to detect the protein expression of cluster of differentiation 31 (CD31), p-AKT and p-extracellular-signal-regulated kinases (Erk). Vaccarin significantly promoted HMEC-1 proliferation and migration and tube formation of HMEC-1 at a dose of 2.15 μM. In vivo, vaccarin delivered by daily oral administration significantly improved epidermal growth factor-induced angiogenesis in an intradermal inoculation mouse model. The mouse Matrigel model study also revealed that vaccarin significantly promoted neovascularization via detection of CD31 levels and enhanced protein expression of p-Akt and p-Erk. In addition, vaccarin also promoted expression of CD31. [ABSTRACT FROM AUTHOR]

Dried stem bark from Albizia julibrissin (AJ) is a highly valued Traditional Chinese Medicine, which has been shown to suppress tumor growth and angiogenesis. Total saponins from AJ (TSAJ) are one of the most bioactive components of AJ extract. The present study evaluated the anti-tumor and anti-angiogenic effects of TSAJ in vitro and in vivo. The anti-angiogenic activity of TSAJ was investigated by measuring the effects on vascular endothelial growth factor (VEGF)-induced proliferation, migration and tube formation of Ea.hy926 endothelial cells in vitro. The expression levels of proteins associated with VEGF-induced angiogenesis were determined by western blotting. Furthermore, in vivo Matrigel™ plug and H22 hepatoma tumor models were used to verify the anti-angiogenic effects of TSAJ. The present study demonstrated that TSAJ significantly inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation of Ea.hy926 cells in vitro. The anti-angiogenic effects of TSAJ were modulated by suppression of phosphorylated-(p-) focal adhesion kinase, p-Akt, and p-extracellular signal-regulated kinase in the VEGF/VEGF receptor 2 (R2) signaling pathway. Furthermore, oral administration of TSAJ significantly inhibited tumor growth and tumor-induced angiogenesis, as well as the formation of functional vessels, in the Matrigel™ plug model. These results suggest that TSAJ may be a potentialpotential anti-angiogenic agent that targets the VEGF/VEGFR2 signaling pathway, and inhibits tumor-induced angiogenesis. [ABSTRACT FROM AUTHOR]