Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

Clinical study of the relationship between cellular adhesion molecules and left ventricular geometry and function in patients with obstructive sleep apnea syndrome and prehypertension / 中华超声影像学杂志

Objective:To investigate the correlations between serum E selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and left ventricular geometry and function in patients with obstructive sleep apnea syndrome (OSAS) combined with prehypertension (pre-HT).Methods:A total of 462 patients with pre-HT and OSAS diagnosed by polysomnography (PSG) in the sleep monitoring unit of the Department of Respiratory and Critical Care Medicine at the First Hospital of Shanxi Medical University from July 2019 to July 2022 were restrospectively analysed, and 52 patients with pure pre-HT (pre-HT group) and 73 patients with pure OSAS (OSAS group) in the same period were selected as the control group. OSAS and pre-HT patients were divided into four groups according to left ventricular geometry: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group and concentric hypertrophy (CH) group. The general clinical data, PSG parameters, blood biochemical parameters and left ventricular structure and function parameters were compared among the six groups. Pearson correlation and multivariate Logistic regression were used to analyze the correlation between E-selection, ICAM-1, VCAM-1, general clinical data, PSG parameters, blood biochemical parameters with left ventricular geometry and function.Results:①Serum E selectin, ICAM-1, and VCAM-1 concentrations increased sequentially from the NG, CR, and EH to CH groups, with the most significant increase in CH group (all P<0.05). In addition, there were statistically significant differences in age, body mass index (BMI), OSAS severity, neck circumference, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), Glu, lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), percentage of time with oxygen saturation below 90% of total sleep time (T90), left ventricular end-diastolic diameter (LVEDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), relative ventricular wall thickness (RWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic flow velocity/peak mitral late diastolic flow velocity (E/A), E wave deceleration time (DT), A wave duration (AD), and isovolumic relaxation time (IVRT), and overall long-axis longitudinal strain (GLS) and so on(all P<0.05). ②Pearson correlation analysis showed that E selectin was negatively correlated with LVEF, E/A, e′, E/e′, IVRT, and GLS ( r=-0.236, -0.131, -0.224, -0.215, -0.285, -0.336; all P<0.05). ICAM-1 was negatively correlated with LVEF, E, E/A, e′, IVRT, and GLS( r=-0.130, -0.129, -0.104, -0.351, -0.252, -0.259; all P<0.05). VCAM-1 was negatively correlated with E, e′, and IVRT ( r=-0.132, -0.312, -0.387; all P<0.001). ③Multifactorial logistic regression analysis showed that E selectin and VCAM-1 were independently correlated with EH (β=1.139, OR=3.124, P=0.030; β=1.288, OR=3.626, P<0.001) and with CH (β=1.178, OR=3.248, P=0.013; β=1.108, OR=3.028, P<0.001). Conclusions:E selection and VCAM-1 were independently correlated with hypertrophic left ventricular geometry, suggesting that E selectin and VCAM-1 may be involved in the process of abnormal left ventricular structure and function in patients with OSAS combined with pre-HT.

Change of serum D-D, sVCAM-1 and P-selectin after limb fractures surgery and their relationship with thrombosis / 中国医师杂志

Objective:To investigate the relationship between change of serum D-dimer (D-D), soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin and thrombosis after limb fracture surgery.Methods:289 patients with limb fractures who were treated in the emergency department of Shulan (Hangzhou) Hospital from January 2021 to January 2022 were selected as the study subjects. They were divided into deep vein thrombosis (DVT) group ( n=62) and non-DVT group ( n=227) according to whether DVT occurred after operation. The levels of prothrombin time (PT), activated partial prothrombin time (APTT), D-D, sVCAM-1 and P-selectin were measured before and after operation in all patients. The levels of PT, APTT, D-D, sVCAM-1 and P-selectin were compared between DVT group and non-DVT group. Logistic sequential stepwise regression analysis was used to analyze the risk factors of postoperative thrombosis in patients with limb fractures. Results:There was no statistically significant difference in PT and APTT between 289 patients with limb fractures after operation and before operation (all P>0.05), while the levels of serum D-D, sVCAM-1 and P-selectin after operation were higher than that before operation (all P<0.05). There was no significant difference in general data between DVT group and non-DVT group (all P>0.05); There was no statistically significant difference in PT and APTT before and after operation between DVT group and non-DVT group (all P>0.05). The levels of serum D-D, sVCAM-1 and P-selectin before and after operation in DVT group were higher than those in non-DVT group (all P<0.05). Logistic sequential stepwise regression analysis showed that high levels of D-D, sVCAM-1 and P-selectin were risk factors for thrombosis after limb fracture surgery (all P<0.05). Conclusions:High levels of D-D, sVCAM-1 and P-selectin are risk factors for thrombosis after limb fracture surgery.

The expression of adhesion molecules in Z310 cells induced by combined exposure to black carbon and lead / 中国职业医学

Objective: To investigate the effects of combined exposure to black carbon and lead on the expression of cell adhesion molecules and their regulating microRNAs (miRNAs) in the rat choroid plexus epithelial Z310 cells. Methods: i) Z310 cells were randomly divided into control group, black carbon exposure group, lead exposure group and combined exposure group. The lead exposure group and black carbon exposure group were treated with 10 μmol/L lead acetate and 10 mg/L black carbon, respectively, and the combined exposure group was treated with both in the above doses. After 12.0 hours, the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) in Z310 cells was detected by Western blotting. The expression of miR-326, miR-328-3p and miR-542-3p which regulated ICAM-1 was detected by real-time fluorescent quantitative polymerase chain reaction. ii) Z310 cells or Z310 cells transfected with miRNA-326 mimic were randomly divided into control group, miRNA-326 transfection control group, combined exposure group and miRNA-326 transfection combined exposure group. Cells in the two control groups were not treated. The two combined exposure groups were treated with 10 mg/L black carbon and 10 μmol/L lead acetate for 12.0 hours. The expression of ICAM-1 was detected by Western blotting. Results: i) The relative expression of ICAM-1, VCAM-1 and MAdCAM-1 in the cells of black carbon exposure group and ICAM-1 in the lead exposure group was higher than those in the control group (all P<0.05). The relative expression of ICAM-1 and MAdCAM-1 in the combined exposure group was higher than those in the other three groups (all P<0.05). The relative expression of VCAM-1 in cells of combined exposure group was higher than those in the control group and lead exposed group (all P<0.05). The relative expression of miR-326 in cells of the lead exposure group and black carbon exposure group was lower than those in the control group (all P<0.05). The relative expression of miR-326 in the combined exposure group was lower than that in the other three groups (all P<0.05). There was no significant difference between miR-328-3p and miR-542-3p in the four groups (all P>0.05). ii) The relative expression of ICAM-1 in cells of the miR-326 transfection control group cells was lower than that in the control group (P<0.05), while in the cells in the combined exposure and miRNA-326 transfection combined exposure group, it was higher than that in the control and miRNA-326 transfection control groups (all P<0.05), and lower in the miRNA-326 transfection combined exposure group than in the combined exposure group (P<0.05). Conclusion: Black carbon or lead exposure can upregulate the expression of ICAM-1, VCAM-1 and MAdCAM-1 in Z310 cells. Black carbon and lead combined exposure lead to a synergistic effect on upregulation of ICAM-1 and MAdCAM-1 expression, particularly ICAM-1. The combined exposure of black carbon and lead may upregulate the expression of ICAM-1 by downregulating the expression of miR-326.

Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bushen Jianpi Jiedu Liyan formula on the expression of integrin alpha 4 beta 1 （α4 β1）， vascular cell adhesion molecule-1 （VCAM-1）， stromal-derived factor-1 （SDF-1）， and chemokine receptor-4 （CXCR4） in the small intestine and bone marrow of the rat model of immunoglobulin A（IgA） nephropathy. MethodA total of 120 male SD rats were used to establish the IgA nephropathy model by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of CCl4， and tail vein injection of lipopolysaccharide （LPS）. The successfully modeled rats were randomized into blank， model， lotensin （63 mg·kg-1）， and low-， medium-， and high-dose （10.4， 20.81， 41.62 g·kg-1， respectively） Bushen Jianpi Jiedu Liyan formula groups （n=16）. The rats were treated with corresponding drugs according to their body weight. After 7 weeks of administration， the rats were sacrificed for the collection of samples， and the protein and mRNA levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the small intestine and bone marrow were determined by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed increased red blood cell count in the urine at the 10th， 12th， 14th， 16th weeks （P<0.01）， and such increases were reduced in the drug intervention groups （P<0.05）， especially in the medium-dose Bushen Jianpi Jiedu Liyan formula group （P<0.05）. Compared with those in the blank group， the protein levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria in the model group were up-regulated （P<0.05）， and such un-regulations were inhibited in the drug intervention groups （P<0.05）. Compared with the model group， medium-dose Bushen Jianpi Jiedu Liyan formula down-regulated the protein levels of SDF-1 and CXCR4 in the intestinal lamina propria （P<0.05）. Compared with the blank group， the model group showed down-regulated mRNA levels of α4 β1 and SDF-1 and up-regulated mRNA levels of VCAM-1 and CXCR4 （P<0.05）. Compared with the model group， the drug intervention groups showed down-regulated mRNA levels of SDF-1 and CXCR4 （P<0.05）. ConclusionBushen Jianpi Jiedu Liyan formula regulates the expression of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria to inhibit the homing effect of plasma cells， which may be associated with the Toll-like receptor-mediated activation of immune response. Bushen Jianpi Jiedu Liyan formula can down-regulate the expression of adhesion molecules to inhibit the proliferation of plasmocytes in circulation， so as to reduce the renal injury of IgA nephropathy.

Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Cornuside ameliorated experimental autoimmune encephalomyelitis by limiting the recruitment of CD4+ T lymphocytes in the spinal cord

We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC

Effects of nano lead oxide exposure on cognitive function and inflammatory mechanism of leukocyte infiltration in mice / 中华行为医学与脑科学杂志

Objective:To investigate the effect of nano lead oxide (nano-PbO) exposure on learning and memory as well as spatial exploration ability in the mice, and the role of leukocyte infiltration of brain tissue in neurobehavioral damage caused by nano-PbO exposure.Methods:A total of 60 male SPF grade Kunming mice were divided into control group, low-dose nano-PbO group, medium-dose nano-PbO group and high-dose nano-PbO group according to body mass matching method, with 15 mice in each group.Mice in low, medium and high dose groups of nano-PbO were intraperitoneally injected with 5 mg·kg -1, 10 mg·kg -1, 20 mg·kg -1 nano-PbO, respectively. And mice in the control group were intraperitoneally injected with the same volume of 0.9% normal saline.The frequency of intervention was once a day for 28 days.Morris water maze test and open field test were used to detect the ability of learning and memory and spatial exploration of mice. Western blot was used to detect the protein expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in hippocampus of mice, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in mouse microvessels and lymphocyte function-associated antigen-1 (LAF-1) in mouse blood leukocyte. The proportion of leukocytes in mouse brain was detected by flow cytometry. All statistical analyses were performed by SPSS 20.0. Morris water maze data were analyzed by repeated measures ANOVA, the other data among multiple groups were compared by one-way ANOVA, and Tukey's test was used for further pairwise comparison.Pearson correlation analysis was performed to evaluate the correlation between neurobehavioral indexes and the proportion of white blood cells, TNF-α and IL-1β in brain tissue. Results:Morris water maze results showed that the escape latency of the four groups of mice had a significant interaction between group and time( F=3.21, P<0.05). The escape latencies of mice in middle and high dose groups of nano-PbO were higher than that in the control group (both P<0.05), and the numbers of crossing the platform of the two groups were lower than that in the control group (both P<0.05). The results of open field test showed that there was a statistically significant difference in the residence time of the mice in the four groups ( F=119.10, P<0.01). The total standing times of mice in the middle group and high dose group of nano-PbO were lower than that in the control group (both P<0.01). The results of Western blot showed that the levels of TNF-α and IL-1β in hippocampus tissue of mice were significant differences among the four groups ( F=7.21, 9.89, both P<0.05). The levels of TNF-α and IL-1β in the hippocampus of mice in the high-dose nano-PbO group were higher than those in the control group (TNF-α: (0.35±0.10), (1.03±0.30), P<0.05; IL-1β: (0.32±0.10), (0.50±0.15), P<0.05). The results of flow cytometry analysis showed that the proportions of leukocytes in the brain tissue of mice in the low, medium and high dose groups of nano-PbO were (9.99±1.09)%, (13.03±0.94)% and (16.51±3.89)%, respectively. Among them, the proportions of leukocytes in the middle and high dose groups of nano-PbO were significantly higher than that in the control group((8.13±1.29)%) (both P<0.05). The results of correlation analysis showed that the proportion of leukocytes, levels of TNF-α, IL-1β protein of hippocampus in the medium, high dose groups of nano-PbO were negatively correlated with the behavioral indexes ( r=-0.815, -0.744, -0.578, all P<0.01; r=-0.771, -0.836, -0.704, all P<0.05; r=-0.823, -0.876, -0.695, all P<0.05). The results of Western blot showed that the levels of ICAM-1 and VCAM-1 in cerebral microvessels of mice in the four groups were significantly different ( F=5.51, 16.19, both P<0.05). The levels of ICAM-1 and VCAM-1 in the middle and high dose groups of nano-PbO were higher than those in the control group(ICAM-1: (1.07±0.16), (1.21±0.35), (0.59±0.19), all P<0.05; VCAM-1: (0.68±0.12), (1.92±0.23), (0.23±0.05), both P<0.05). In addition, there was a significant difference in the level of LFA-1 protein in blood leukocytes of mice in the four groups ( F=41.80, P<0.05). The levels of LFA-1 in the middle and high dose groups of nano-PbO were higher than that in the control group((0.33±0.06), (0.89±0.23), (0.05±0.01), both P<0.05). Conclusion:The nano-PbO exposure can lead to cognitive impairment and increased inflammatory factors in the hippocampus of mice, which may be related to the increase of ICAM-1 and VCAM-1 in vascular endothelial cells, which promotes leukocyte infiltration into brain tissue.

Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)

Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34+ stem cells (6×106 cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

Adhesion molecules before and after propylthiouracil in patients with subclinical hyperthyroidism

SUMMARY OBJECTIVE This study aimed to investigate the effect of propylthiouracil treatment on adhesion molecules in patients with subclinical hyperthyroidism. METHODS In this study, a total of 168 patients diagnosed with subclinical hyperthyroidism were treated with propylthiouracil for one year. The levels of adhesion molecules, consisting of sICAM-1, sVCAM-1, and sE-Selectin, before and after the treatment were measured and compared. These results were compared with the levels of 148 healthy controls who received a placebo. RESULTS sICAM-1 levels were significantly higher in subclinical hyperthyroidism patients than in healthy controls (*pa=0.000). sICAM-1 levels were significantly decreased after the treatment (**pb=0.000). Despite this decrease in patients with subclinical hyperthyroidism, it did not decrease to the level of the control group. sVCAM-1 did not change before and after propylthiouracil treatment. The level of sE-selectin was similar to that of the pretreatment control group, but it did not have statistical significance, although it increased after the treatment (**pb=0.004). CONCLUSION The sICAM level was significantly higher than the pretreatment values and decreased after the propylthiouracil treatment. However, further studies are needed to reduce the risk of atherosclerosis and cancer in patients with subclinical hyperthyroidism.

RESUMO ANTECEDENTES O objetivo deste estudo foi investigar o efeito do tratamento com propiltiouracil nas moléculas de adesão em pacientes com hipertireoidismo subclínico. MÉTODOS Neste estudo, 168 pacientes diagnosticados com hipertireoidismo subclínico foram tratados com propiltiouracil por um ano. Os níveis de moléculas de adesão, especificamente sICAM-1, sVCAM-1 e sE-Selectina, antes e após o tratamento foram medidos e comparados. Esses resultados foram comparados com os níveis de 148 indivíduos saudáveis no grupo de controle que receberam um placebo. RESULTADOS Os níveis de sICAM-1 foram significativamente maiores em pacientes com hipertireoidismo subclínico do que nos controles saudáveis (*pa=0,000). Os níveis de sICAM-1 diminuíram significativamente após o tratamento (**pb=0,000). Apesar dessa diminuição em pacientes com hipertireoidismo subclínico, ela não diminuiu para o nível do grupo controle. O sVCAM-1 não se alterou antes e após o tratamento com propiltiouracil. O nível de sE-Selectina foi semelhante ao do grupo de controle pré-tratamento, mas não apresentou significância estatística, embora tenha aumentado após o tratamento (** pb = 0,004). CONCLUSÃO O nível de sICAM foi significativamente superior aos valores pré-tratamento e diminuiu após o tratamento com propilciliouracil. No entanto, mais estudos são necessários para reduzir o risco de aterosclerose e câncer em pacientes com hipertireoidismo subclínico.

In vivo Mechanical Niches of Vascular Cells / 医用生物力学

The elastic stress and viscous shear stress experienced by the vessel wall under pulse blood pressure and blood flow and the mechanical properties of the substrate constitute the in vivo mechanical niches of vascular cells, and these mechanical stimuli are involved in regulating the biological responses of vascular cells and inducing the remodeling and pathological changes of vascular tissues. Although many experimental studies on vascular mechanobiology have been reported, the quantitative correlation between the mechanical stimuli of in vitro experiments and the physiological and pathological conditions of blood vessels remains to be elucidated. This paper summarized the quantitative evaluation method of in vivo mechanical niches of vascular cells from the viewpoint of biomechanics, and then focused on effects of the physiological locations and aging on mechanical behaviors of the vessel wall. This paper also explored the physiological and pathological characteristics of the cellular mechanical niches and their implications for current vascular mechanobiological studies.

Comparison of sharp dissection, electrocautery, and ultrasonic activated scalpel with regard to endothelial damage, preparation time, and postoperative bleeding during radial artery harvesting

Abstract Objective: To examine the effects of classical technique, electrocautery, and ultrasonic dissection on endothelial integrity, function, and preparation time for harvesting the radial artery (RA) during coronary artery bypass grafting (CABG). Methods: Forty-five patients who underwent isolated CABG and whose RA was suitable for use were studied and divided into three groups: Group 1, classical method (using sharp dissection); Group 2, electrocautery; and Group 3, ultrasonic cautery. Levels of prostacyclin and nitric oxide derivatives were examined biochemically; vascular cell adhesion molecule 1 (VCAM-1) and endothelial nitric oxide synthetase (eNOS) values were assessed using immunohistochemical staining. RA preparation time, RA length/harvesting time ratio, and drainage amounts at the site of RA removal were compared. Results: Differences in RA preparation time (Group 1: 25±6 min, Group 2: 18±3 min, Group 3: 16±3 min, P<0.001) and length/harvesting time ratio (Group 1: 0.76±0.19 cm/min, Group 2: 0.98±0.16 cm/min, Group 3: 1.13±0.09 cm/min, P<0.001) were statistically significant among the groups. Levels of prostacyclin and nitric oxide derivatives were not statistically significant different, VCAM-1 and eNOS expressions were observed to be similar among the groups, and endothelial damage was detected in only one patient per group. Conclusion: Use of ultrasonic cautery during RA preparation considerably reduces the preparation time and postoperative drainage amount. However, the superiority of one method over the others could not be demonstrated when the presence of endothelial damage with both biochemical and histopathological evaluations was considered.

Rg1 alleviates the cholestatic liver fibrosis throughregulation of NF-κB/VCAM-1 / 药学学报

A mouse model of cholestatic liver fibrosis was established by bile duct ligation (BDL) method. The effect of ginsenoside Rg1 in the disease progress and the mechanism of cholestatic liver fibrosis are investigated in this mouse model. All animal experiments in this paper have been approved by the Unit Ethics Committee. Analysis of serum biochemical indicators and pathological sections assessed liver function, liver damage and fibrosis in mice. Immunohistochemistry and Western blot assays were used to detect vascular cell adhesion molecule-1 (VCAM-1) in BDL-induced mice. Nuclear factor-κB (NF-κB) and inflammatory factors were detected to investigate related mechanism of Rg1. The results showed that expression of VCAM-1 was up-regulated and peaked at 7 days, followed by decreased expression, but still efficiently expressed compared to the sham-operated group. Compared with the model group, 40 mg·kg-1·d-1 Rg1 treatment reduced serum aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin (T.Bili) levels (P<0.05 or P<0.01) and liver function damage,alleviated BDL-induced liver fibrosis, significantly down-regulated the expression of VCAM-1 (P<0.05), and inhibited the inflammatory response. In addition, Rg1 significantly reduced NF-κB p65 level in the cellular nucleus (P<0.05). This study demonstrates that VCAM-1 is dynamically altered during BDL-induced liver fibrosis. Rg1 could dampen inflammation and alleviate cholestatic liver fibrosis via regulation of the NF-κB/VCAM-1 pathway. The results provide an experimental basis for Rg1 application for treating liver fibrosis.

Inhibitory effect of peripheral blood iTr35 cells on vascular endothelial cell vascular cell adhesion molecule-1 in children with pulmonary artery hypertension / 中华实用儿科临床杂志

Objective@#To explore the role of iTr35 cells in the pathogenesis of children with pulmonary artery hypertension (PAH) in children, and the percentage of iTr35 cells and serum interleukin(IL)-35 levels in peripheral blood of patients with PAH were investigated.Their inhibitory effects on the expression of vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells were also analyzed.@*Methods@#After 3 mL peripheral blood of 30 congenital heart disease (CHD) patients with PAH, 22 CHD patients without PAH and 30 age or gender matched healthy controls (HC) were collected, the percentage of iTr35 cells were detected by flow cytometry and the concentrations of serum IL-35 were detected by Luminex, as well as soluble VCAM-1 (sVCAM-1). Human pulmonary artery endothelial cells (HPAECs) were cultured in vitro and divided into control group, tumor necrosis factor (TNF)-α group and IL-35+ TNF-α group.The expression of VCAM-1 and nuclear factor(NF)-κB P65 protein of each group were detected by flow cytometry and Western blot.The adhesion of peripheral blood mononuclear cells (PBMCs) to HPAECs was observed by fluorescence microscope.@*Results@#Compared to CHD patients without PAH, the percentage of iTr35 cells[0.86(0.45-1.63)% vs.1.14(0.46-2.11)%](H=20.52, P<0.05) in peripheral blood and serum IL-35 levels[2.43(1.76-2.85) μg/L vs.3.17(2.92-5.66) μg/L](H=119.56, P<0.05) were significantly decreased in CHD patients with PAH.However, serum sVCAM-1 concentration[923.1(892.6-1 118.7) μg/L vs.776.1(743.5-932.3) μg/L ] in CHD patients with PAH were significant increased (H=65.65, P<0.05). In addition, the concentration of serum IL-35 were negatively correlated with sVCAM-1 in PAH patients (r=-0.374 P=0.042). In vitro, the positive rate of VCAM-1 on HPAECs was significant decreased in IL-35+ TNF-α group as compared to the TNF-α group [(2.07±0.82)% vs.(5.83±1.34)%, F=1 197.18, P<0.05]. In addition, the protein expression of NF-κB P65 in HPAECs was significantly decreased in TNF-α+ IL-35 group as compared to TNF-α group, as well as the adhesion of PBMCs to HPAECs (F=212.04, 2 533.51, all P<0.05).@*Conclusions@#The percentages of iTr35 and levels of IL-35 are reduced in the peripheral blood of patients with PAH.Through in vitro experiments, IL-35 is found to reduce PBMCs adhesion by inhibiting VCAM-1 expression in HPAECs.

The effect of alpha-lipoic acid on expression of VCAM-1 in type 2 diabetic rat / 대한해부학회지

Correlation of serum sICAM-1 and sVCAM-1 levels with severity of and prognosis of thyroid-associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the correlation between levels of serum soluble intercellular adhesion molecule-1(sICAM-1), soluble vascular cell adhesion molecule-1(sVCAM-1)and the severity of thyroid-associated ophthalmopathy(TAO). <p>METHODS: A total of 120 patients with TAO admitted to the hospital from August 2016 to March 2018 were selected and included in the study. According to the clinical activity score(CAS), the patients were divided into active stage group and inactive stage group. According to the severity, they were divided into mild group, moderate group and severe group. There were 90 healthy persons were selected as the control group at the same time. The general data, serum sICAM-1 and sVCAM-1 levels were compared among groups and the correlation of sICAM-1 and sVCAM-1 levels with the severity of TAO was analyzed. <p>RESULTS: There were no significant differences in the clinical basic data of patients in between the different clinical active stage groups and the control group, and between the different severity groups and the control group(<i>P</i>>0.05). The levels of serum sICAM-1 and sVCAM-1 in the active stage group were significantly higher than those in the inactive stage group and the control group(<i>P</i><0.01). The levels of serum sICAM-1 and sVCAM-1 in active stage patients of different severity groups were significantly higher than those in inactive stage patients and of control groups(<i>P</i><0.01). There were no significant differences in levels of serum sICAM-1 and sVCAM-1 in inactive stage patients of different severity groups. The levels of serum sICAM-1 and sVCAM-1 in active stage patients of different severity groups increased gradually with the severity of the disease. There was no significant correlation between levels of serum sICAM-1 and sVCAM-1 in inactive stage patients and the severity of disease(<i>r</i>=0.102, 0.095, <i>P</i>=0.135, 0.167). Levels of serum sICAM-1 and sVCAM-1 in active stage patients were positively correlated to severity of disease(<i>r</i>=0.695, 0.824, <i>P</i>=0.005, 0.002).<p>CONCLUSION: The levels of serum sICAM-1 and sVCAM-1 in inactive patients will not increase with the severity of the disease. However, the levels in patients with active disease will increase with the severity of the disease, which can be used for clinical diagnosis and staging of TAO and monitoring of the prognosis.

Inhibitory effect of peripheral blood iTr35 cells on vascular endothelial cell vascular cell adhesion molecule_1 in children with pulmonary artery hypertension / 中华实用儿科临床杂志

Objective To explore the role of iTr35 cells in the pathogenesis of children with pulmonary artery hypertension(PAH)in children,and the percentage of iTr35 cells and serum interleukin(IL)_35 levels in peripheral blood of patients with PAH were investigated. Their inhibitory effects on the expression of vascular cell adhesion mole_cule_1(VCAm_1)on vascular endothelial cells were also analyzed. Methods After 3 mL peripheral blood of 30 congenital heart disease( CHD)patients with PAH,22 CHD patients without PAH and 30 age or gender matched healthy controls(HC)were collected,the percentage of iTr35 cells were detected by flow cytometry and the concentra_tions of serum IL_35 were detected by Luminex,as well as soluble VCAm_1(sVCAm_1). Human pulmonary artery endothelial cells(HPAECs)were cultured in υitro and divided into control group,tumor necrosis factor( TNF)_α group and IL_35+TNF_α group. The expression of VCAm_1 and nuclear factor( NF)_κB P65 protein of each group were detected by flow cytometry and Western blot. The adhesion of peripheral blood mononuclear cells(PBmCs) to HPAECs was observed by fluorescence microscope. Results Compared to CHD patients without PAH,the percent_age of iTr35 cells[0. 86(0. 45_1. 63)% υs. 1. 14(0. 46_2. 11)%](H=20. 52,P<0. 05)in peripheral blood and serum IL_35 levels[2. 43(1. 76_2. 85)μg/L υs. 3. 17(2. 92_5. 66)μg/L]( H=119. 56,P<0. 05)were signifi_cantly decreased in CHD patients with PAH. However,serum sVCAm_1 concentration[923. 1(892. 6_1 118. 7)μg/L υs. 776. 1(743. 5_932. 3)μg/L ]in CHD patients with PAH were significant increased( H=65. 65,P<0. 05). In addition,the concentration of serum IL_35 were negatively correlated with sVCAm_1 in PAH patients(r= _0. 374 P=0. 042). In υitro,the positive rate of VCAm_1 on HPAECs was significant decreased in IL_35+TNF_α group as compared to the TNF_α group[(2. 07 ± 0. 82)% υs.(5. 83 ± 1. 34)%,F=1 197. 18,P<0. 05]. In addition,the protein expression of NF_κB P65 in HPAECs was significantly decreased in TNF_α+IL_35 group as compared to TNF_α group,as well as the adhesion of PBmCs to HPAECs(F=212. 04,2 533. 51,all P<0. 05). Conclusions The percentages of iTr35 and levels of IL_35 are reduced in the peripheral blood of patients with PAH. Through in υitro ex_periments,IL_35 is found to reduce PBmCs adhesion by inhibiting VCAm_1 expression in HPAECs.

A preliminary study on the biomimetic drug delivery system targeting atherosclerotic lesions / 药学学报

Based on the natural affinity between macrophages and atherosclerotic lesions, we made a novel macrophage membrane-coated polylactic acid-glycolic acid copolymer (PLGA) nanoparticle (MPLNPs), and examined its ability targeting atherosclerotic lesions. PLGA nanoparticle (PLGANPs) were prepared by precipitation and MPLNPs were prepared by membrane extrusion. Their morphology, particle size and retainment of functional proteins were characterized. Their targeting capabilities were investigated with cell uptake assay in vitro and fluorescence imaging in vivo. The results showed that MPLNPs were spherical, with obvious core/shell structure, the average particle size was (167 ±6.12) nm, and integrin α4β1 was retained on the surface. Vascular cell adhesion molecule 1 (VCAM-1) receptor was highly expressed in the LPS (lipopolysaccharides)-HUVEC (human umbilical vein endothelial cells) and atherosclerotic lesions in ApoE-/- mouse model, and the nanoparticles could effectively recognize the VCAM-1 receptor and had good targeting properties in vitro and in vivo. The results suggest that the cell membrane biomimetic nano-carrier may provide a new approach for the targeting strategy in the treatment of atherosclerosis and related diseases.

Clinical effect of Shenqi-Tongmai decoction in stable angina pectoris patients with Qi-deficiency-blood-stasis syndrome and the influence on levels of serum associated adhesion factors / 国际中医中药杂志

Objective To investigate the effect of Shenqi-Tongmai decoction in Stable Angina pectoris Patients with Qi-deficiency-blood-stasis syndrome and the influence on serum associated adhesion factors. Methods A total of 110 patients with stable angina pectoris treated in the department of cardiology of traditional Chinese medicine hospital of Xinle city from Feb. 2015 to Feb. 2017 were divided into 2 groups according to the number random table method, with 55 in each group. All the patients were given the standardized treatment with western medicine, and the treatment group were aditionally treated with the Shenqi-Tongmai decoction. All the patients were treated for a course of 4 weeks. The TCM syndrome score, Seattle angina questionnaire (SAQ) score, electrocardiographic examination index and serum soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) level of the two groups before and after treatment were compared, and the clinical curative effect of the two groups was compared. Results The TCM syndrome score (7.1 ± 2.2 vs. 11.4 ± 3.0, t=8.590), serum sICAM-1 (227.69 ± 42.81 ng/ml vs. 275.33 ± 48.62 ng/ml, t=5.454) level, serum sVCAM-1 (272.04 ± 39.87 ng/ml vs. 296.58 ± 42.60 ng/ml, t=3.127) level and lead ecg ST segment down number (2.7 ± 0.6 vs. 3.2 ± 0.6, t=4.067), T wave of low lead numbers (1.7 ± 0.3 vs. 2.1 ± 0.3, t=6.807), numbers of T wave inversion lead (1.7 ± 0.3 vs. 2.1 ± 0.2, t=9.908) of the treatment group were significantly lower than those of the control group (P<0.01). The SAQ scores (76.8 ± 10.5 vs. 67.4 ± 10.1, t=4.805) was higher than that of the control group (P<0.01). The curative effect of angina pectoris and electrocardiogram of the treatment group were 91.0% (50/55) and 92.7%(51/55), and the control group were 76.4% (42/55) and 78.2% (43/55). The difference was statistically significant between the two groups (χ2=4.251, 4.681, P<0.05). Conclusions Traditional Chinese medicine Shenqi-Tongmai decoction can effectively improve the SAQ scores and TCM syndrome score and electrocardiogram examination index, improve the clinical curative effect in the treatment of Stable Angina pectoris based on the western medicine (Qi-deficiency-blood-stasis syndrome) and its mechanism may be related to improving of the serum levels of sICAM 1, sVCAM 1.

The effect of periodontal therapy on neopterin and vascular cell adhesion molecule-1 levels in chronic periodontitis patients with and without acute myocardial infarction: a case-control study

Abstract The presence of neopterin in gingival crevicular fluid (GCF) is a marker for local and acute immune activation, and the presence of vascular cell adhesion molecule (VCAM-1) in GCF is accepted as a marker for chronic vascular inflammation. Objectives This study aimed to evaluate effects of periodontal treatment on GCF levels of neopterin and VCAM-1 in patients with chronic periodontitis (CP) with acute myocardial infarction (AMI) compared with systemically healthy CP patients. Material and methods Sixty subjects (20 CP patients with AMI, 20 healthy CP patients, and 20 healthy controls) were included. GCF samples were analyzed at baseline and after 3 and 6 months, and the probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing, gingival (GI) and plaque (PI) indices were recorded. We determined neopterin and VCAM-1 levels (concentration and total amount) using enzyme-linked immunosorbent assay (ELISA). No significant differences were seen between the AMI+CP and CP groups for PI, GI, GCF levels of neopterin and VCAM-1 at baseline. Results The number of teeth with 5 mm≤CAL<7 mm and CAL≥7 mm were significantly increased in the AMI+CP group at baseline. There were no significant differences between the AMI+CP and CP for PI, CAL, GCF volumes, and the AMI+CP group had the highest clinical improvement in the number of teeth with 5 mm≤CAL<7 mm at the sixth month. There were significant positive correlations between clinical periodontal inflammation and the presence of neopterin and VCAM-1 in GCF prior to and following periodontal treatment, and between the GCF volume and clinical parameters. Conclusions Data suggest that the total amount and concentration of neopterin and VCAM-1 in GCF seemed to be closely associated with periodontal disease severity in CP patients with AMI. Moreover, the results of our study demonstrate that the past periodontal status is potentially correlated between groups, with similar periodontal disease severity.