Hydrogen Activates ATP-Binding Cassette Transporter A1-Dependent Efflux Ex Vivo and Improves High-Density Lipoprotein Function in Patients With Hypercholesterolemia: A Double-Blinded, Randomized, and Placebo-Controlled Trial.

Context: We have found that hydrogen (dihydrogen [H2]) decreases plasma low-density lipoprotein (LDL) cholesterol levels and improves high-density lipoprotein (HDL) function in patients with potential metabolic syndrome in a before-after self-controlled study.

Objective: The purpose of this study was to further characterize the effects of H2-rich water (0.9 L/day) on the content, composition, and biological activities of plasma lipoproteins on patients with hypercholesterolemia and their underlying mechanisms in a double-blinded, randomized, and placebo-controlled trial.

Chitosan Oligosaccharides Attenuate Atherosclerosis and Decrease Non-HDL in ApoE-/- Mice.

Aim: Chitosan-oligosaccharides (COS) treatment showed lipid lowering effects in rats and reverse cholesterol transport (RCT) promotion in mice, suggested that COS might be a potential atheroprotective material. In this study, we investigated the effects of COS treatment on atherosclerosis (AS) in apolipoprotein E deficient mice (apoE-/-).

Methods: After feeding high fat (HF) diet for 12 weeks with the gastric gavages administration of COS or vehicle, respectively, the mice were sacrificed for the assessment of atherosclerosis, plaque stability, and the mechanism investigation.

D4F alleviates macrophage-derived foam cell apoptosis by inhibiting CD36 expression and ER stress-CHOP pathway.

This study was designed to explore the protective effect of D4F, an apoA-I mimetic peptide, on oxidized LDL (ox-LDL)-induced endoplasmic reticulum (ER) stress-CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) pathway-mediated apoptosis in macrophages. Our results showed that treating apoE knockout mice with D4F decreased the serum ox-LDL level and apoptosis in atherosclerotic lesions with concomitant downregulation of cluster of differentiation 36 (CD36) and inhibition of ER stress. In vitro, D4F inhibited macrophage-derived foam cell formation.

Cardioprotective Effect of Hydrogen-rich Saline on Isoproterenol-induced Myocardial Infarction in Rats.

Background: Infusion with hydrogen gas-saturated saline has recently been reported to exert antioxidant and anti-inflammatory activity that may protect against organ damage induced by oxidative stress. Therefore because oxidative stress plays a significant role in the pathophysiology of myocardial infarction (MI), the aim of our study was to investigate whether hydrogen-rich saline has cardioprotective effects against isoproterenol-induced MI in rats.

Methods: An acute MI model was induced in male Wistar rats by subcutaneous injection of isoproterenol.

[Endoplasmic reticulum stress mediates oxidized low density lipoprotein-induced scavenger receptor A1 upregulation in macrophages].

The present study was to investigate whether endoplasmic reticulum stress (ERS) was involved in oxidized low density lipoprotein (ox-LDL)-induced scavenger receptor A1 (SR-A1) upregulation in macrophages. RAW264.7 cells were pretreated with 20 mmol/L of 4-phenylbutyric acid (PBA) for 30 min and then treated with ox-LDL (50 mg/L) for 12 h or stimulated with 2 mg/L tunicamycin (TM) or 2 μmol/L thapsigagin (TG) for 4 h.

Phospholipid transfer protein destabilizes mouse atherosclerotic plaque.

Objective: Phospholipid transfer protein (PLTP) accelerates the development of atherosclerosis in mouse models. We examined the role of PLTP in atherosclerotic plaque stability.

Approach And Results: We prepared apolipoprotein E and PLTP double-knockout (PLTP(-/-)ApoE(-/-)) mice.

[Ox-LDL down-regulates expression of pigment epithelium-derived factor in human umbilical vein endothelial cells].

Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti-inflammatory, antioxidant and antithrombotic properties and plays a protective role against atherosclerosis (AS). The purpose of the present study is to explore the effects of oxidized low density lipoprotein (ox-LDL) on the expression of PEDF in cultured human umbilical vein endothelial cells (HUVECs). HUVECs were cultured and incubated with ox-LDL at different concentrations (6.

Phospholipid transfer protein in diabetes, metabolic syndrome and obesity.

It has been reported that phospholipid transfer protein (PLTP) is an independent risk factor for human coronary artery disease. And metabolic tissues are important contributors to the systemic pools of PLTP protein. Consistently, PLTP mass and activity have been found to be elevated in the plasma of type 2 diabetes mellitus (T2DM) and obese patients.

Niacin inhibits vascular inflammation via downregulating nuclear transcription factor-κB signaling pathway.

The study aimed to investigate the effect of niacin on vascular inflammatory lesions in vivo and in vitro as well as its lipid-regulating mechanism. In vivo study revealed that niacin downregulated the levels of inflammatory factors (IL-6 and TNF-α) in plasma, suppressed protein expression of CD68 and NF-κB p65 in arterial wall, and attenuated oxidative stress in guinea pigs that have been fed high fat diet. In vitro study further confirmed that niacin decreased the secretion of IL-6 and TNF-α and inhibited NF-κB p65 and notch1 protein expression in oxLDL-stimulated HUVECs and THP-1 macrophages.

Ethanol extract of propolis protects endothelial cells from oxidized low density lipoprotein-induced injury by inhibiting lectin-like oxidized low density lipoprotein receptor-1-mediated oxidative stress.

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), as the primary oxidized low-density lipoprotein (ox-LDL) receptor on endothelial cells, plays a crucial role in endothelial injury, which is a driving force in the initiation and development of atherosclerosis. Our previous studies have shown that ethanol extract of propolis (EEP) promotes reverse cholesterol transport and inhibits atherosclerotic lesion development. However, the protective effects of EEP against ox-LDL-induced injury in endothelial cells and the underlying mechanisms are still unknown.

Emodin accentuates atrial natriuretic peptide secretion in cardiac atria.

Emodin, an active anthraquinone constituent isolated from the rhubarb, a traditional Chinese herbal medicine which is widely used in clinical treatment, has cardiovascular protective properties. However, it remains unclear whether the cardiovascular protective actions of emodin are related to an activation of cardiac natriuretic hormone secretion. The purpose of the present study was to explore the effect of emodin on the secretion of ANP, a member of the family of cardiac natriuretic hormones, and its mechanisms involved.

D-4F, an apolipoprotein A-I mimetic peptide, protects human umbilical vein endothelial cells from oxidized low-density lipoprotein-induced injury by preventing the downregulation of pigment epithelium-derived factor expression.

Aim: To investigate the protective effects of D-4F, an apolipoprotein A-I mimetic peptide, on oxidized low-density lipoprotein (ox-LDL)-induced injury of vascular endothelial cells and the potential role of pigment epithelium-derived factor (PEDF).

Methods: Cytotoxicity was assessed by the apoptotic rate, 3-(4,5-dimethylthiazol-2-y-l)-2,5-diphenyl-2H-tetrazolium bromide assay, and lactate dehydrogenase release. PEDF levels were analyzed with Western blot and quantitative real-time polymerase chain reaction.

Galactomannan with novel structure produced by the coral endophytic fungus Aspergillus ochraceus.

The homogeneous extracellular polysaccharide, AW1, was obtained from the fermented broth of the fungus Aspergillus ochraceus derived from coral Dichotella gemmacea. AW1 was a galactomannan with a molar ratio of mannose and galactose of 2.16:1.

Higher level of plasma bioactive molecule sphingosine 1-phosphate in women is associated with estrogen.

Both sphingosine 1-phosphate (S1P) and estrogen have been documented to play endothelial protective roles. However, it remains unclear whether estrogen could regulate the anabolism of the bioactive molecule S1P and the underlying mechanisms. In this study, 108 healthy participants were separated into three age groups, and their plasma S1P levels were analyzed by liquid chromatography tandem mass spectrometry.

Phospholipid transfer protein (PLTP) deficiency impaired blood-brain barrier integrity by increasing cerebrovascular oxidative stress.

Phospholipid transfer protein (PLTP) regulates lipid metabolism and plays an important role in oxidative stress. PLTP is highly expressed in blood-brain barrier (BBB), but the role of PLTP in BBB integrity is not clear. In this study, BBB permeability was detected with in vivo multiphoton imaging and Evans blue assay.

Endoplasmic reticulum stress promotes macrophage-derived foam cell formation by up-regulating cluster of differentiation 36 (CD36) expression.

Oxidized low-density lipoprotein (ox-LDL) up-regulates CD36, a scavenger receptor responsible for macrophage uptake of ox-LDL without limitation. However, the precise underlying mechanism is not completely understood. Our previous study has demonstrated that ox-LDL induces endoplasmic reticulum (ER) stress in macrophages.

Phospholipid transfer protein deficiency decreases the content of S1P in HDL via the loss of its transfer capability.

Sphingosine-1-phosphate (S1P) is an amphiphilic signaling molecule, which is enriched in functional high density lipoprotein (HDL) and shows arterial protection. The distribution of S1P is changed with increased plasma phospholipid transfer protein (PLTP) activity and impaired HDL function in patients with coronary heart diseases. Therefore, we hypothesized that PLTP might transfer S1P among cells or lipoproteins.

PLTP deficiency impairs learning and memory capabilities partially due to alteration of amyloid-β metabolism in old mice.

Increased expression of phospholipid transfer protein (PLTP) was observed in the brains of Alzheimer's disease (AD) patients; however, the role of PLTP in the progress of AD is still poorly understood. The objective of this study was to evaluate the effect of PLTP deficiency on the recognition and metabolism of amyloid-β (Aβ) in mice. We performed the Morris water maze to determine the learning and memory capabilities of 50-week age wild type mice (WT, n = 12) and PLTP knockout mice (PLTP-/-, n = 12).

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome.

We have found that hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters. The objective of this study was to characterize the effects of H2-rich water (0.9-1.

Celastrus orbiculatus Thunb. decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed high fat diet.

Celastrus orbiculatus Thunb. (COT), a traditional Chinese herb, has anti-inflammatory and anti-oxidative properties. In this study, we examined the protective effect of COT on the initiation of atherosclerosis induced by high fat diet and explored the underlying mechanisms.

Apolipoprotein A-I mimetic peptide reverse D-4F improves the biological functions of mouse bone marrow-derived late EPCs via PI3K/AKT/eNOS pathway.

Apolipoprotein A-I (ApoA-I) mimetic peptide inhibits the development of atherosclerosis (AS) in apolipoprotein E-deficient mice; however, the underlying mechanism remains unclear. Endothelial progenitor cells (EPCs) can prevent AS progression through repairing proatherogenic factors impaired endothelium. In the present study, we examined the effect of reverse D-4F, one of apoA-I mimetic peptide on the proliferation, migration, and tube formation of mouse bone marrow-derived late EPCs.

[Inhibitory effect of quercetin preconditioning on tunicamycin-induced apoptosis in macrophages and its mechanism].

The purposes of the present study were to investigate the inhibitory effect of quercetin (QUE) preconditioning on endoplasmic reticulum stress (ERS) inducer tunicamycin (TM)-induced apoptosis in RAW264.7 macrophages and the underlying molecular mechanisms. RAW264.

Inhibitory effect of the combination therapy of simvastatin and pinocembrin on atherosclerosis in ApoE-deficient mice.

Unlabelled: The present study was performed to investigate the effects of the combination therapy of pinocembrin and simvastatin on the atherosclerotic lesions development in the ApoE-/- mice.

Methods: Eight-week-old male ApoE-/- mice were fed high fat diet (HFD) and treated with simvastatin (10 mg/kg per day), pinocembrin (20 mg/kg per day), or the combination therapy (simvastatin 5 mg/kg per day and pinocembrin 20 mg/kg per day) for 14 weeks. The serum lipid levels, nitric oxide (NO), endothelin (ET), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined with spectrophotometric measurement and ELISA assay.

Pinocembrin, a major flavonoid in propolis, improves the biological functions of EPCs derived from rat bone marrow through the PI3K-eNOS-NO signaling pathway.

The number and quality of endothelial progenitor cells (EPCs) are damaged to varying degrees in patients at risk for developing atherosclerosis. The improvement of the quantity and functions of EPCs can enhance repair of injured endothelial monolayer resulting in inhibiting atherosclerosis. The purpose of this study was to investigate the effect of pinocembrin (PIN), a major flavonoid in propolis on the differentiation and biological functions of EPCs and the potential mechanisms of these effects.

Activating transcription factor 6 mediates oxidized LDL-induced cholesterol accumulation and apoptosis in macrophages by up-regulating CHOP expression.

Aim: This study was to explore whether activating transcription factor 6 (ATF6), an important sensor to endoplasmic reticulum (ER) stress, would mediate oxidized low-density lipoprotein (ox-LDL)- induced cholesterol accumulation and apoptosis in cultured macrophages and the underlying molecular mechanisms.

Methods: Intracellular lipid droplets and total cholesterol levels were assayed by oil red O staining and enzymatic colorimetry, respectively. Cell viability and apoptosis were determined using MTT assay and AnnexinV-FITC apoptosis detection kit, respectively.