Atherosclerotic cardiovascular disease (ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice (RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.
Apoptosis ; drug effects ; Atherosclerosis ; pathology ; physiopathology ; prevention & control ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Cardiovascular Diseases ; pathology ; physiopathology ; prevention & control ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Endothelium, Vascular ; cytology ; drug effects ; physiology ; Humans ; Inflammation ; prevention & control ; Lipid Metabolism ; drug effects ; Oxidative Stress ; drug effects

OBJECTIVEThis study observed attenuating effect of hydroxysafflor yellow A (HSYA), an effective ingredient of aqueous extract of Carthamus tinctorius L, on lipopolysaccharide (LPS)-induced endothelium inflammatory injury.

METHODSEahy926 human endothelium cell (EC) line was used; thiazolyl blue tetrazolium bromide (MTT) test was assayed to observe the viability of EC; Luciferase reporter gene assay was applied to measure nuclear factor-κB (NF-κB) p65 subunit nuclear binding activity in EC; Western blot technology was used to monitor mitogen activated protein kinase (MAPKs) and NF-κB activation. Reverse transcription polymerase chain reaction (RT-PCR) method was applied to observe intercellular cell adhesion molecule-1 (ICAM-1) and E-selectin mRNA level; EC surface ICAM-1 expression was measured with flow cytometry and leukocyte adhesion to EC was assayed with Rose Bengal spectrophotometry technology.

RESULTSHSYA protected EC viability against LPS-induced injury (P <0.05). LPS-induced NF-κB p65 subunit DNA binding (P <0.01) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) phosphorylation was inhibited by HSYA. HSYA attenuated LPS triggered ICAM-1 and E-selectin mRNA levels elevation and phosphorylation of p38 MAPK or c-Jun N-terminal kinase MAPK. HSYA also inhibited LPS-induced cell surface ICAM-1 protein expression P <0.01) and leukocyte adhesion to EC (P <0.05).

CONCLUSIONHSYA is effective to protect LPS-induced high expression of endothelium adhesive molecule and inflammatory signal transduction.

Cell Adhesion ; drug effects ; Cell Nucleus ; drug effects ; metabolism ; Cell Survival ; drug effects ; Chalcone ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; E-Selectin ; genetics ; metabolism ; Endothelium, Vascular ; drug effects ; pathology ; Gene Expression Regulation ; drug effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; pathology ; Humans ; I-kappa B Proteins ; metabolism ; Inflammation ; drug therapy ; pathology ; Intercellular Adhesion Molecule-1 ; genetics ; metabolism ; Leukocytes ; cytology ; drug effects ; Lipopolysaccharides ; MAP Kinase Signaling System ; drug effects ; NF-KappaB Inhibitor alpha ; Phosphorylation ; drug effects ; Protective Agents ; pharmacology ; Protein Binding ; drug effects ; Quinones ; chemistry ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism

Oxidized low density lipoprotein (oxLDL) can trigger intracellular production of reactive oxygen species and lipid peroxidation (LPO), and is thought to contribute to initiation and progression of atherosclerosis. In order to understand the correlation between oxLDL and macromolecular damage, we measured levels of LPO-derived miscoding etheno-DNA adducts and LPO-modified proteins in cultured human vascular endothelial and smooth muscle cells after incubation with oxLDL for up to 48 h. A semi-quantative analysis method for 1, N6-ethenodeoxyadenosine (ɛdA) by immunohistochemistry was applied. After oxLDL stimulation, ɛdA-stained nuclei were significantly increased in both endothelial and smooth muscle cells. Similarly, 4-hydroxy-2-nonenal (4-HNE)-modified proteins, as analyzed by immunohistochemistry and Western blotting, were also 3-5 fold increased. It was concluded LPO-derived etheno-DNA adducts and LPO-modified proteins are strongly induced by oxLDL in human vascular endothelial and smooth muscle cells. This macromolecular damage may contribute to the dysfunction of arterial endothelium and the onset of atherosclerosis.
DNA ; metabolism ; Endothelium, Vascular ; cytology ; drug effects ; metabolism ; Humans ; Lipid Peroxidation ; drug effects ; Lipoproteins, LDL ; pharmacology ; Muscle, Smooth ; cytology ; drug effects ; metabolism ; Proteins ; metabolism

The aim of this study was to investigate whether shear stress could promote function of endothelial progenitor cells (EPCs) with Shexiang Baoxin Pill (SBP) treatment in vitro, and to study whether shear stress contributed to vascular injury repair by EPCs. EPCs were isolated and characterized; EPCs' proliferation, migration, adhesion, tube formation and eNOS protein level in vitro were investigated by culturing confluent EPCs in 4 mg/mL SBP under physiological shear stress (15 dyne/cm2) for up to 24 hours. Afterwards, EPCs were transfused into rats after wire-induced carotid artery injury augmented re-endothelialization. The results showed that, compared to the SBP group, the shear stress+SBP group obviously enhanced EPCs proliferation, migration, adhesion, tube formation and eNOS protein expression in vitro (P<0.01). After one week, immunofluorescence staining showed that endothelial regeneration rate obviously enhanced in shear stress+SBP group (P<0.01). The present study demonstrates that shear stress can promote function of endothelial progenitor cells treated with SBP, which improves the vascular injury repair potentials of EPCs.
Animals ; Cell Adhesion ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Progenitor Cells ; cytology ; drug effects ; Endothelium, Vascular ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; Regeneration ; Stress, Mechanical

In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.
Antioxidants ; chemical synthesis ; metabolism ; pharmacology ; Cells, Cultured ; Curcuma ; chemistry ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Endothelium, Vascular ; cytology ; drug effects ; metabolism ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Hydrogen Peroxide ; metabolism ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Oxidation-Reduction ; Oxidative Stress ; drug effects ; Phthalic Acids ; chemical synthesis ; pharmacology ; Sesquiterpenes ; chemical synthesis ; pharmacology ; Succinates ; chemical synthesis ; pharmacology ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the vasodilating effect of adrenomedullin 2 (ADM2) by antagonizing angiotensin 1 (Ang II), and to explore its mechanism.

METHODSEighteen male, 180-200 g SD rats were randomly divided into 3 groups (n = 6): control group, Ang II (150 ng/(kg x min)) group and Ang II (150 ng/(kg x min)) + ADM2(500 ng/(kg x h)) group. Mini-osmotic pumps filled with peptide were implanted in the back of rats subcutaneously. After two weeks, the blood pressure was measured by the way of carotid intubation. The plasma was collected for the detection of nitric oxide (NO) content and the activity of endothelial nitric oxide synthase (eNOS). The in situ oxidation of fluorescent dye dihydroethidium (DHE) was used for detecting superoxide in rat arteries. The rat isolated arterial rings were made for studying the vasodilating effect of ADM2. Human umbilical vein endothelial cell line EA. hy 926 cells were cultured and their intracellular reactive oxygen species (ROS) were evaluated by probe DCFH-DA.

RESULTSADM2 dramatically decreased the blood pressure in angiotensin II-induced hypertension rat model, enhanced plasma NO content and the activity of eNOS and reduced superoxide formation in vessel walls. ADM2 also induced relaxation of the vascular rings preconstricted by Ang II in a concentration-dependent and endothelium-dependent manner. In cultured vascular endothelium, ADM2 ameliorated the ROS generation induced by Ang II.

CONCLUSIONAdrenomedullin 2 relaxed blood vessels by antagonizing angiotensin II-induced oxidative stress and improving the vascular endothelial function.

Adrenomedullin ; pharmacology ; Angiotensin II ; pharmacology ; Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; Drug Antagonism ; Endothelium, Vascular ; drug effects ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Male ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; blood ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Vasodilation ; drug effects

OBJECTIVETo investigate the effects of non-neuronal muscarinic receptors (NNMR) stimulation on atherosclerosis and endothelial cells activation.

METHODSAtherosclerosis model was established in ApoE-/- mice by a high fat diet for 7 weeks. During the experimental periods, animals were received a low (7 mg/kg/d) or a high (21 mg/kg/d) dose of arecoline by gavage. At the termination of the treatments, serum total cholesterol and NO levels were measured, and the aorta morphology was analyzed by hematoxylin and eosin staining. The gene expression of monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in the thoracic aortas was determined by RT-PCR, and the MCP-1 protein expression and NF-κB activity were detected by Western blot analysis. NO production, MCP-1 secretion in cultured rat aortic endothelial cells (RAECs), and monocyte-endothelium adhesion assay were also performed after arecoline treatments.

RESULTSArecoline efficiently decreased atherosclerotic plaque areas, increased serum nitric oxide (NO) content, suppressed the mRNA and protein expression of MCP-1, and modulated the IκB-α degradation and P65 phosphorylation in the aortae of ApoE-/- mice. Furthermore, arecoline promoted NO production and suppressed MCP-1 secretion in cultured RAECs after ox-LDL exposure, and either atropine or NG-nitro-L-arginine methylester could abrogate these effects. Arecoline also significantly inhibited the adherence of U937 monocytes to the ox-LDL injured human umbilical vein endothelial cells, which could be abolished by atropine.

CONCLUSIONOur results indicate that arecoline attenuates the progression of atherosclerosis and inhibits endothelial cells activation and adherence by stimulating endothelial NNMR. These effects, at least in part, are due to its modulation on NF-κB activity.

Animals ; Aorta ; cytology ; Apolipoproteins E ; Arecoline ; pharmacology ; Atherosclerosis ; physiopathology ; prevention & control ; Cell Adhesion Molecules ; metabolism ; Chemokine CCL2 ; metabolism ; Cholesterol ; blood ; Disease Progression ; Endothelial Cells ; cytology ; drug effects ; Endothelium, Vascular ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; I-kappa B Proteins ; metabolism ; Lipoproteins, LDL ; Mice ; Mice, Knockout ; Monocytes ; cytology ; NF-KappaB Inhibitor alpha ; Nitric Oxide ; blood ; Nitroarginine ; pharmacology ; Rats ; Receptors, Muscarinic ; physiology ; Transcription Factor RelA ; metabolism

OBJECTIVETo explore the new mechanism of propranolol for treatment of hemangioma and the effects of propranolol on proliferation of hemangioma-derived mesenchymal stem cells ( Hem- MSCs).

METHODSWe isolated Hem-MSCs from hemangioma in the proliferating phase by their selective adhesion to plastic culture dishes. Immunofluorescence staining was used to examine the expression of marker antigens in Hem-MSCs. Human umbilical vein endothelial cells(HUVECs) were used as control. Indiuction of multi-lineage differentiation including osteogenesis and adipogeneis was performed with appropriate medium to identify the multi-lineage differentiation potential. MTT cell counting was used to observe the effects of different concentrations of propranolol on proliferation of Hem-MSCs.

RESULTSHem- MSCs were fibroblast-like morphology. All of them expressed vimentin, most expressed α-SMA,CD133, some expressed Glutl, and none of them expressed VEGF. Osteogenic, adipogenic differentiations of Hem- MSCs were induced successfully. Effects of low concentration of propranolol on proliferation of Hem-MSCs were not obvious, while high concentration of propranolol can inhibit the proliferation of Hem-MSCs.

CONCLUSIONSThe cells we isolated from hemangioma are Hem-MSCs. High concentration of propranolol can inhibit the proliferation of Hem-MSCs.

Adipogenesis ; Antigens ; metabolism ; Cell Differentiation ; Cell Proliferation ; drug effects ; Cells, Cultured ; Endothelium, Vascular ; cytology ; Fibroblasts ; cytology ; Hemangioma ; pathology ; Humans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; metabolism ; Osteogenesis ; Propranolol ; pharmacology ; Umbilical Veins ; Vimentin ; metabolism

OBJECTIVETo discuss the effect of Taohong Siwu Decoction (TSD) in regulating functions of endothelial cells and treating arteriosclerosis obliterans (ASO).

METHODSThe ASO model was prepared by using high-fat diet plus intimal injury. They were randomly divided into the model group (n = 10), the normal control group (n = 9), the low dose TSD group (group A, n = 12), the middle dose TSD group (group B, n = 10), and the high dose TSD group (group C, n = 9). Eight weeks after modeling, the limb blood perfusion was observed using laser Doppler flowmetry. The arterial morphology was observed using light microscope and transmission electron microscope. The number of circulating endothelial cells (CECs) was determined using Percoll density gradient centrifugation method. Serum levels of TNF-alpha, IL-1, ET-1, and NO were detected using double antibody sandwich assay of enzyme linked immunosorbent assay (ELISA).

RESULTSThe ASO rat model was successfully established. Blood lipids levels significantly increased, the blood perfusion of left hind limbs significantly decreased, the number of CECs in the peripheral blood significantly increased, the arterial lumen was irregularly narrowed, the ultra-structure of vessel walls was damaged, serum levels of TNF-alpha, IL-1, and ET-1 significantly increased, and the serum level of NO significantly decreased in the model group, showing statistical difference when compared with the normal control group (P < 0.01). Compared with the model group, significant improvement in the aforesaid indices was shown in group B and C (P < 0.05, P < 0.01).

CONCLUSIONSThe injury and abnormal functions of endothelial cells is an important pathological process of ASO. As an effective recipe for treating ASO, TSD could protect vascular endothelial cells and improve the secretion function of vascular endothelial cells.

Animals ; Arteriosclerosis Obliterans ; blood ; drug therapy ; Diet, High-Fat ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endothelial Cells ; metabolism ; Endothelin-1 ; blood ; Endothelium, Vascular ; cytology ; Interleukin-1 ; blood ; Male ; Nitric Oxide ; blood ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the protective effects of hepatocyte growth factor (HGF) on hypoxic human pulmonary microvascular endothelial cells (HPMECs).

METHODSHPMECs were cultured in vitro, and the hypoxic model was established by the physical method. Cells were divided into 4 groups: the control group, the hypoxic group, HGF group, and phytohemagglutinin (PHA) group. The 7(th) generation of HPMECs was evaluated by the method of immunocytochemistry. The persistence rate of HPMECs was measured by MTT assay and the adhesive cells were counted by the microscopy. The expression of intercellular adhesion molecule-1 (ICAM-1) protein was determined by immunofluorescence staining.

RESULTSThe adherence percentage of cells significantly decreased after hypoxia, whereas the expression of the ICAM-1 protein was significantly higher in the hypoxia group than in control group (P<0.01). Compared with the hypoxia group, the persistence and adherence percentage of cells in the HGF group significantly increased (P<0.01), whereas the expression of the ICAM-1 protein significantly dropped (P<0.01). In the PHA group, the persistence and adhesion rate were significantly different from those in the hypoxia group and HGF group (P<0.01), and the expression of the ICAM-1 protein increased significantly (P<0.01).

CONCLUSIONHGF could inhibit the hypoxic damage of HPMECs by decreasing the persistence and the adhesive capacity of these cells and inducing the expression of ICAM-1.

Cell Adhesion ; drug effects ; Cell Hypoxia ; Cell Survival ; drug effects ; Cells, Cultured ; Endothelial Cells ; drug effects ; Endothelium, Vascular ; cytology ; metabolism ; Hepatocyte Growth Factor ; pharmacology ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Lung ; blood supply