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

Endothelial Cells ; pathology ; Endothelium, Vascular ; cytology ; pathology ; Humans ; Mucocutaneous Lymph Node Syndrome ; pathology

OBJECTIVE: We evaluated the effect of close contact between the stent and the graft on the induction of endothelial covering on the stent graft placed over an aneurysm. MATERIALS AND METHODS: Saccular abdominal aortic aneurysms were made with Dacron patch in eight dogs. The stent graft consisted of an inner stent, a expanded polytetrafluoroethylene graft, and an outer stent. After sacrificing the animals, the aortas with an embedded stent graft were excised. The aortas were inspected grossly and evaluated microscopically. RESULTS: The animals were sacrificed at two (n = 3), six (n = 3), and eight months (n = 2) after endovascular repair. In two dogs, the aortic lumen was occluded at two months after the placement. On gross inspection of specimens from the other six dogs with a patent aortic lumen, stent grafts placed over the normal aortic wall were covered by glossy white neointima, whereas, stent grafts placed over the aneurysmal aortic wall were covered by brownish neointima. On microscopic inspection, stent grafts placed over the normal aortic wall were covered by thin neointima (0.27 +/- 0.05 mm, mean +/- standard deviation) with an endothelial layer, and stent grafts placed over the aneurysmal aortic wall were covered by thick neointima (0.62 +/- 0.17 mm) without any endothelial lining. Transgraft cell migration at the normal aortic wall was more active than that at the aneurysmal aortic wall. CONCLUSION: Close contact between the stent and the graft, which was achieved with stent grafts with endo-exo-skeleton, could not enhance endothelial covering on the stent graft placed over the aneurysms.
Animals ; Aortic Aneurysm, Abdominal/pathology/*therapy ; Blood Vessel Prosthesis Implantation ; Disease Models, Animal ; Dogs ; Endothelium, Vascular/cytology/pathology ; *Stents ; Tomography, X-Ray Computed

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 evaluate the effects of aminoguanidine on methylglyoxal-mediated oxygen-glucose deprivation (OGD) injury in the cultured human brain microvascular endothelial cells (HBMEC).

METHODSCultured HBMEC cells were pretreated with methylglyoxal before oxygen-glucose deprivation injury. Cell vitality was determined by MTT method, cell mortality was assessed by LDH release method, cell apoptosis was examined by Annexin V/PI formation method, and the advanced glycation end products (AGEs) were detected by Western-blot.

RESULTSMethylglyoxal induced HBMEC injury in a dose-dependent manner. At 2 mmol/L of methylglyoxal, the cell viability was 56.1% when methylglyoxal-pretreated cells exposed to oxygen-glucose deprivation, the cell inhibition rate was 90.0%. Aminoguanidine (1 mmol/L) inhibited methylglyoxal and OGD induced LDH release and Annexin V/PI formation. Furthermore, aminoguanidine (1 mmol/L) also decreased advanced glycation end products (AGEs) formation induced by methylglyoxal and oxygen-glucose deprivation.

CONCLUSIONAminoguanidine protected methylglyoxal mediated-oxygen-glucose deprivation injury in the cultured HBMEC, which may be associated with anti-glycation activity.

Apoptosis ; drug effects ; Cell Hypoxia ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Drug Antagonism ; Endothelial Cells ; drug effects ; metabolism ; pathology ; Endothelium, Vascular ; cytology ; Glycation End Products, Advanced ; metabolism ; Guanidines ; pharmacology ; Humans ; Pyruvaldehyde ; pharmacology

OBJECTIVETo investigate the possible involvement of erythr opoietin (EPO)/erythropoietin receptor (EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR).

METHODSEPOR positive circulating progenitor cells (CPCs: CD34(+)) and endothelial progenitor cells (EPCs: CD34(+)KDR(+)) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients with out diabetes ( n=7),non-proliferative DR (NPDR, n=7),non-proliferative DR (PDR, n=8), and PDR complicated with diabetic nephr opathy (PDR-DN, n=7).

RESULTSThe numbers of EPOR(+) CPCs and EPOR(+) EPCs were reduced remarkably in NPDR compared with the control group (both Pü0.01), whereas rebounded in PDR and PDR-DN groups in varyingdegrees. Similar changes were observed in respect of the proportion of EPOR(+)CPCs in CPCs (NPDR vs. control, Pü0.01) and that of EPOR(+) EPCs in EPCs (NPDR vs. control, Pü0.05).

CONCLUSIONExogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the impaired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR(+)EPCs associated with ischemia.

Aged ; Cell Count ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Retinopathy ; pathology ; Endothelium, Vascular ; cytology ; Erythropoietin ; blood ; Female ; Humans ; Male ; Middle Aged ; Receptors, Erythropoietin ; analysis ; Stem Cells ; physiology

OBJECTIVETo evaluate the effect of endothelial progenitor cells (EPCs) mobilization on the healing of calvarial defect in diabetic mice.

METHODS55 type II adult male diabetic mice were included in this study. They were randomly divided into three groups: the non-operative group (n = 5), the experimental group (n = 25) and the control group (n = 25). Two circular bony defects, 3 mm in diameter, were created on the parietal bones of the diabetic mice. Intraperitoneal AMD3100 (10 mg/kg; n = 25) or sterile saline (control group) was administered daily beginning at post-operative day 3 and continuing for 15 days. 5 mice were sacrificed in each group at non-operation, post-operative week 1,2,4, 8,12. Circulation EPC level was measured at pre-operation, post-operative day 7 and day 14. Bony regeneration was assessed with micro-CT at post-operative week 4, 8 and 12. HE staining was performed on all the decalcified bone samples. Immunofluorescent CD31 and osteocalcin staining was performed on calvarial defects at weeks 1, 2, and 4 to assess the vascularity and osteoblast density, respectively.

RESULTSThe mobilization of EPC in diabetic mice almost disappeared one week after trauma, while AMD3100 could dramatically increase the circulation EPC level for a long time after trauma. Compared to control group, the healing percentage of bony defect in the diabetic mice treated with AMD3100 was obviously increased at post-operative week 8 (50.5% vs. 34.8%) and week 12 (50.9% vs. 40.2%). Calvarial defects of AMD3100-treated mice harvested at 1, 2, and 4 weeks demonstrated increased vascularity and osteoblast density, compared to the controls. The difference was most marked in postoperative week 2 (vascularity: 6.11% vs. 2.47%; osteoblast density 2.81% vs. 1.22%, P < 0.01).

CONCLUSIONAMD3100 can improve the healing of calvarial defect in diabetic mice by increasing the vascularity and osteoblast density at the regeneration area.

Animals ; Bone Regeneration ; Diabetes Mellitus, Experimental ; Endothelial Cells ; cytology ; drug effects ; Endothelium, Vascular ; cytology ; Heterocyclic Compounds ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Osteoblasts ; cytology ; Parietal Bone ; Skull ; pathology ; Stem Cells ; cytology ; drug effects ; Wound Healing

Endothelium, Vascular ; cytology ; Humans ; Mucocutaneous Lymph Node Syndrome ; complications ; pathology ; Neovascularization, Pathologic ; Stem Cells ; cytology

OBJECTIVETo observe the effects of Tongguan Capsule on the mobilization and differentiation of bone marrow mononuclear cells (BMMNCs) to the injured carotid arteries.

METHODSThe rat model of injured carotid arteries was established. Mononuclear cells were separated from the bone marrow of donor rats, which were labeled by PKH 26 and then injected through the tail vein to the recipient rats with injured carotid arteries. The rats were randomly divided into two groups. Tongguan Capsule suspension was administered by gastrogavage to rats in the experiment group, while equal volume of normal saline was given to rats in the control group. Four weeks later the injured carotid arteries were harvested and frozen sections were made to observe the differences of intima area/media area ratio (Ai/Am). The difference of BMMNCs migrating to the injured carotid arteries between the two groups was observed under fluorescence microscope. The difference of the vascular endothelial growth factor (VEGF) and stromal derived factor-1 (SDF-1) levels in serum were detected by ELISA.

RESULTSThe PKH 26 labeled cells appeared in the experiment group, while only little scattered fluorescent light points was presented in the control group. The intima area and the ratio of Ai/Am of the experiment group decreased more obviously than that of the control group (P<0.01). Two and 4 weeks later the VEGF and SDF-1 levels in serum of the experiment group were more obviously enhanced than those of the control group (P<0.01).

CONCLUSIONTongguan Capsule could promote the BMMNCs transplanting towards the intima of injured carotid arteries, and take part in the repair of the intima of injured carotid arteries.

Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Chemokine CXCL12 ; blood ; Drugs, Chinese Herbal ; pharmacology ; Endothelium, Vascular ; Monocytes ; cytology ; drug effects ; Rats ; Rats, Wistar ; Tunica Intima ; cytology ; drug effects ; pathology ; Vascular Endothelial Growth Factor A ; blood