Endothelial Microparticles: Markers of Inflammatory Response After Sutureless Valve Implantation

ABSTRACT Introduction: Systemic inflammatory response syndrome (SIRS) is related to increased circulating endothelial microparticles (EMP). Objective: The aim of this study was to compare the plasma concentration of EMP between patients undergoing aortic valve replacement with conventional bioprosthesis implantation and Perceval™ S (LivaNova) and to evaluate its impact on the inflammatory response in the short-term follow-up. Methods: This is a randomized clinical trial with 24 patients submitted to isolated aortic valve replacement divided into two groups: Perceval™ S (Group P) and conventional bioprostheses (Group C). Incidence of severe SIRS (three or more criteria) in the first 48 hours postoperatively, EMP release profile, interleukins (IL) 6 and 8, C-reactive protein, and procalcitonin were analyzed preand postoperatively at 24 hours and three months. Results: There were 24 patients (12 in each group), mean age was 69.92±5.17 years, 83.33% were female, the incidence of severe SIRS was 66.7% and 50% in groups C and P, respectively (P=0.68), and EMP showed a significant increase in the 24-hour postoperative period (P≤0.001) and subsequent decrease in the three-month postoperative period (P≤0.001), returning to baseline levels. For IL-6 and IL-8, there was a greater increase in group C at 24 hours postoperatively (P=.0.02 and P<0.001). Conclusion: The incidence of severe SIRS was similar in both groups, with significantly higher levels of IL-6 and IL-8, at the 24-hour postoperative period, in group C, however with higher levels of EMP in group P, and subsequent return to baseline levels at the three-month postoperative period in both groups.

Changes and formation mechanism of plasma endothelial microparticles in patients with acute pancreatitis / 临床肝胆病杂志

Objective To investigate the changes and formation mechanism of plasma endothelial microparticles (EMPs) in patients with acute pancreatitis (AP). Methods Blood samples were collected from 60 patients with AP who were treated in The First Affiliated Hospital of Anhui Medical University from August 2020 to June 2021, and these patients were divided into mild acute pancreatitis (MAP) group with 23 patients, moderate-severe acute pancreatitis (MSAP) group with 23 patients, and severe acute pancreatitis (SAP) group with 14 patients; 20 individuals who underwent physical examination were enrolled as control group.Differential centrifugation was used to obtain platelet-poor plasma, flow cytometry was used to measure the level of CD31 + CD41 - EMPs, and ELISA was used to measure the levels of endothelin-1(ET-1), von Willebrand factor (vWF), nitric oxide (NO), and vascular cell adhesion molecule-1(VCAM-1).HUVECs were stimulated by the plasma of AP patients, and then flow cytometry and qRT-PCR were used to measure the changes in EMPs, reactive oxygen species (ROS), and mitochondrial membrane potential and the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1(ICAM-1), VCAM-1, NADPH oxidase, and P-selectin.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups and within each group.The chi-square test was used for comparison of categorical data between groups, and the Pearson correlation test was used for correlation analysis. Results Compared with the control group, the MAP, MSAP, and SAP groups had a significant increase in the level of EMPs (all P < 0.05).Compared with the MAP and MSAP groups, the SAP group had a significant increase in the level of EMPs (both P < 0.05).In the patients with AP, the level of EMPs was negatively correlated with Acute Physiology and Chronic Health Evaluation Ⅱ score, Bedside Index for Severity in Acute Pancreatitis, Ranson score, CT score, and C-reactive protein ( r =0.686 2, 0.777 3, 0.713 8, 0.771 8, and 0.473 9, all P < 0.01).Compared with the control group, the MAP, MSAP, and SAP groups had significant increases in the levels of ET-1, vWF, and VCAM-1 and a significant reduction in the level of NO (all P < 0.05).Compared with the control group, the MSAP and SAP groups had the plasma that promoted the release of a large amount of EMPs (both P < 0.05).Compared with the control group, all the other groups, except the MAP group in terms of VCAM-1 and eNOS, had significant increases in the mRNA expression levels of eNOS, iNOS, ICAM-1, P-selectin, VCAM-1, and NADPH oxidase (all P < 0.05).Compared with the HC group, the MAP, MSAP, and SAP groups and the LPS group had a significant increase in the level of ROS and a significant reduction in mitochondrial membrane potential in HUVECs (all P < 0.05). Conclusion There is a significant increase in the plasma level of EMPs in AP patients, which is correlated with the severity of pancreatitis.Meanwhile, the plasma of AP patients can promote the formation of EMPs in HUVECs in vitro, which may be associated with cell oxidative injury.

Potency biomarker effect of Endothelial Microparticles (EMPs) for early prediction of cardiovascular risk in shift worker nurses

Objectives@#Shift work results in changing worker’s behavior, food, and sleep patterns, which can cause circadian rhythm disturbance, which is a cardiovascular risk. Until now, a biomarker of early prediction of cardiovascular risk on shift workers is still not developed. This study aimed to assess the cardiovascular risk of shift worker nurses by detecting endothelial microparticles (EMPs). @*Methods@#This longitudinal study compared six shift nurses and five non-shift nurses by measuring the EMPs using antigen CD31+ flow cytometry. All met the inclusion criteria consisting of 28 blood samples followed in one week shift. @*Results@#EMPs among non-shift nurses were below 200 μL. However, shift nurses’ EMPs increased above 200 μL with Man-Whitney U p = 0.000 on days 4 and 7 following a one shift per week schedule. @*Conclusion@#There was an increase in shift workers’ endothelial microparticles (EMP) which was a sign of cardio-vascular risk.

Effect of Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma Extract on HUVECs Senescence Mediated by Endothelial Microparticles / 中国实验方剂学杂志

Objective:To investigate the effect of Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma extract on endothelial microparticles （EMPs）-induced vascular endothelial cell senescence， and explore the possible mechanism. Method:Human umbilical vein endothelial cells （HUVECs） were used as the research objects， and the aged model was established with 10-12 passages of replicative senescence cells. The experimental cells were divided into young group （2-4 passage cells）， aged group （10-12 passage cells）， only EMPs intervention group （extract EMPs produced by aged cells to intervene young cells） and low dose， middle dose and high dose drug intervention groups （200， 300， 400 mg·L^-1）. Senescence related <italic>β</italic>-galactosidase （SA-<italic>β</italic>-gal） staining and cell cycle propidium iodide （PI） staining were used to determine cell senescence. Cell counting kit-8 （CCK-8） assay was used to screen the drug concentration. EMPs were extracted by two-step centrifugation， EMPs labeled with phycoerythrin （PE） anti-human CD31 antibody or fluorescein isothiocyanate （FITC） annexin V were detected by flow cytometry， intracellular reactive oxygen species （ROS） were detected by 2'，7'- dichlorofluorescein diacetate （DCFDA） staining. Result:After treatment with the drug， SA-<italic>β</italic>-gal activity of the aged cells significantly decreased （<italic>P</italic><0.01）， the S phase arrest was restored （<italic>P</italic><0.01）， and the number of CD31⁺ EMPs and annexin V⁺ EMPs secreted by aged cells decreased （<italic>P</italic><0.05）. Compared with the young group， only EMPs intervention group could induce increased SA-<italic>β</italic>-gal activity and S phase arrest in young cells （<italic>P</italic><0.05，<italic>P</italic><0.01）. However， after intervention of EMPs and the drug， EMPs-mediated increase of SA-<italic>β</italic>-gal activity was significantly inhibited and S phase arrest was restored （<italic>P</italic><0.05）. The increase of intracellular ROS induced by EMPs was also significantly inhibited by the drug （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma extract can delay the senescence of vascular endothelial cells by influencing EMPs， and the mechanism may be related to the inhibition of increased intracellular ROS induced by EMPs.

Correlation between endothelial microparticles and subacute 1,2-dichloroethane toxic encephalopathy / 中国职业医学

OBJECTIVE: To explore the correlation between endothelial microparticles(EMPs) and subacute 1,2-dichloroethane(1,2-DCE) toxic encephalopathy. METHODS: A total of 24 patients with subacute 1,2-DCE toxic encephalopathy were selected as the case group, and 24 healthy individuals were selected as the control group using a convenient sampling method. Blood plasma was collected from the fasting venous blood of patients in these two groups, and the level of EMPs in the plasma was detected by flow cytometry. RESULTS: The levels of plasma EMPs of patients in the control group and the case group were(692.0±174.4) ×10~3/L and(839.8±155.8) ×10~3/L respectively. The levels of plasma EMPs in patients with mild, moderate and severe case subgroups were(691.6±101.9) ×10~3/L,(900.6±46.6) ×10~3/L and(1 026.8±69.8)×10~3/L respectively. The EMPs level of patients in the case group was higher than that of the control group(P<0.01). The level of EMPs in the moderate and severe case subgroups was higher than that of the control group and mild case subgroup(P<0.01). CONCLUSION: Endothelial injury was found in patients with subacute 1,2-DCE toxic encephalopathy and endothelial injury is related to the severity of poisoning.

Circulating microparticles and central blood pressure according to antihypertensive strategy

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Clinical implication of changes of circulating endotheliao microparticles in burned patients / 中华创伤杂志

Objective To evaluate the clinical implication of circulating endothelial microparticles in severe burned patients in burn shock resuscitation period and in patients with severe infection.Methods A retrospective case control study was conducted on 90 burned patients from January 2009 to December 2015.The patients were divided into burn shock group (n =57) and infection group (n =33).The infection group was further divided into sepsis group (n =18) and non sepsis group (n=15).There were 17 healthy controls.The numbers of CD31 +,CD51 +,CD144 +,CD54 +,and CD62E + EMPs in plasma were measured by flow cytometry immediately thereafter.The numbers and ratios of EMPs in plasma of the 16 patients from burn shock group were compared before and after fluid resuscitation.The numbers and ratios of EMPs in plasma were compared among groups.Sequential Organ Failure Assessment (SOFA) scores were used to assess the burn severity in patients at enrollment.The numbers and ratios of EMPs in plasma were compared between sepsis and non sepsis group.The correlations of SOFA with the numbers of EMPs and with the burn size were analyzed.Results Compared with control group,the numbers of CD31 +,CD51 +,CD144 +,CD54 +,and CD62E + EMPs were increased significantly in both burn shock group and infection group (P ＜0.05 or ＜0.01);the ratios of CD31 + EMPs,CD51 + EMPs,and CD54 + EMPs in plasma were significantly higher in burn shock group (P＜O.05 or ＜0.01);the ratios of CD31 + EMPs and CD54 + EMPs were significantly higher in infection group (P ＜ 0.05 or ＜ 0.01).The number of CD62E + EMPs,the ratios of CD144 + EMPs and CD62E + EMPs were higher in burn shock group than those in infection group (P ＜0.05 or ＜0.01).The ratio of CD31 + EMPs in plasma was significantly higher before resuscitation than that after resuscitation in burn shock period patients (8.8 ± 1.7 vs.5.2 ±0.9) (P ＜0.05).The ratios of CD31 + EMPs and CD54 + EMPs were significantly higher in sepsis group than those in non-sepsis group (8.0± 1.3 vs.4.5 ± 1.0;18.3 ± 2.2 vs.8.9 ± 1.4) (P ＜ 0.05 or ＜ 0.O1).The number of antigen-positive EMPs correlated significantly with SOFA score (P ＜0.05 or ＜0.01).The ratio of CD54 + EMPs correlated significantly with SOFA score (P ＜0.01).The number and the ratio of CD54 + EMPs as well as the ratio of CD144 + EMPs was correlated with bum size (P ＜ 0.05).SOFA score was positively correlated with the burn size (P ＜ 0.01).Conclusions Expressions of CD31,CD54,CD144,CD62E antigens EMPs might play a role in burn pathological damage and serve as an indicator of endothelium function change after bums.Expression of CD54 of EMPs plays a role in assessing the function and severity of burned organs.

The role of endothelial microparticles in Beh(c)et's disease / 中华风湿病学杂志

Objective Endothelial microparticles (EMPs) are direct indicator of endothelial cell activation or apoptosis,and may also reflect endothelial inflammation,increased coagulation,and vascular tone.The aim of this study is to investigate whether EMPs would be able to evaluate systemic involvement and be a new indicator of disease activity in Beh(c)et's disease (BD).Methods Thirty-nine consecutive BD patients (who fulfilled the modified International Study Group on BD in 1990 or International Criteria for BD in 2006) and 67 age and sex-matched healthy controls were enrolled (Including 37 patients with hypertension and 30 healthy subjects).The plasma levels of EMPs were measured by flow cytometry utilizing specific labels for endothelial MPs (CD31+ and CD42b-).The measurement data of each group were expressed as-x±s,and the comparison data betwen groups were analyzed by independent sample t test and analysis of variance,Spearman/Pearson correlation analysis,P＜0.05 was statistically significant.Results The levels of circulating EMPs (CD31 + and CI42b-) were significantly elevated in the case group compared with the healthy control group and hypertension (F=6.845,P＜0.05).Moreover,BD patients plasma EMPs were positively correlated with active BD (r=0.802,P＜0.05).Vascular involvement in BD patients was higher than in patients without vascular EMPs,t=4.707,P＜0.05.Gastrointestinal involvement in BD patients was more frequent than that in patients without Gastrointestinal involvement,t=2.673,P＜0.05.Conclusion Levels of circulating EMPs are elevatedd in BD patients and correlated with disease activity in BD.Elevated EMPs may be a potential indicator to predict disease activity of BD.The plasma level of EMPs is increased,which indicats increased risk of vascular and digestive tract involvement in BD.

Relationship of CD31+/CD42b- and CD144+ endothelial micropaticles with intima-media thickness of carotid artery / 西安交通大学学报(医学版)

Objective To detect the levels of CD31+/CD42b- and CD144+ endothelial microparticles (EMPs)in plasma,and analyze the relationship with carotid intima-media thickness (CIMT)and the risk factors of atherosclerosis.Methods Totally 122 outpatients and inpatients in our hospital were selected,and carotid artery ultrasound examination was performed.The results were divided into a thickening group (62 cases)and a control group (60 cases).Flow cytometry was used to detect the levels of CD31+/CD42b- and CD144+ EMPs in the blood to analyze the relationship between the level of endothelial cells and CIMT,and to investigate the relationship between the level of plasma EMPs and the risk factors of atherosclerosis.Results Compared with the control group,the levels of EMPs of CD31+/CD42b- and CD144+ were significantly higher.In the correlation analysis, plasma CD31+/CD42b- and CD144+EMPs levels were positively correlated with CIMT;in multi-factor Logistic regression analysis,CD31+/CD42b- EMPs levels were correlated positively with age,TC and Cys C;plasma CD144+ EMPs levels were correlated with UA and BMI.Conclusion The levels of CD31+/CD42b-,CD144+EMPs in plasma were correlated with CIMT,guiding early prevention of cardiovascular diseases.

Influence of tongxinluo on blood endothelial microparticles and MMP-9 in patients with acute myocardial infarction after percutaneous coronary intervention / 重庆医学

Objective To study influence of tongxinluo on blood endothelial microparticles(EM Ps) and matrix metalloprotei‐nase‐9(MMP‐9) in patients with acute myocardial infarction after percutaneous coronary intervention(PCI) .Methods One hundred and twenty‐eight hospitalized patients with acute myocardial infarction after per‐cutaneous coronary intervention were recruited from January 2012 to December 2014 ,All patients were randomly divided into tongxinluo group (n=65) and control group (con‐ventional treatment ,n=63) .Tongxinluo group was on the basis of conventional treatment group with tongxinluo capsules 2 plus ,3 times a day .We detected the EMPs and MMP‐9 of two groups preoperatively and on the 7th postoperatively day .Results Com‐pared with the conventional treatment group ,blood EMPs and MMP‐9 in tongxinluo group were lower after 7 days treatment ,the difference was statistically significant (P<0 .05) .There was a positive correlation between the EMPs and MMP‐9(P<0 .05) .Con‐clusion For patients with acute myocardial infarction after percu‐taneous coronary intervention ,tongxinluo could further inhibit in‐flammatory reaction ,make the plaque stability and improve the function of endothelial cells on the basis of conventional treatment groups .

Relationship between endothelial microparticles and CD4+CD25+Foxp3+ regulatory T cells in patients with acute coronary syndrome / 吉林大学学报(医学版)

Objective:To explore the relationships between the endothelial microparticles (EMPs)in peripheral blood and CD4+ CD25 + Foxp3+ regulatory T cells and their cytokine levels in the patients with acute coronary syndrome (ACS),and to clarify the mechanism of EMPs in the pathogenesis of ACS by affecting the Treg cell differentiation and function.Methods:Twenty-three patients with stable angina (SAP)were allocated to SAP group,and 52 patients with ACS were allocated to ACS group.Twenty individuals with normal conventional coronary angiography results were recruited as control group.The levels of EMPs and the percents of CD4+ CD25 +Foxp3+ regulatory T cells in peripheral blood of the patients in various groups were measured by flow cytometry. The expressions of Foxp3 mRNA and the plasma levels of TGF-β1 were detected with Real-Time PCR and ELISA, respectively.Correlation analysis was performed between EMPs and regulatory T cells,Foxp3 mRNA expression level and TGF-β1 level.Results:Compared with control group and SAP group,the level of EMPs in peripheral blood of the patients in ACS group was increased significantly,but the percentage of regulatory T cells,the Foxp3 mRNA expression level and the plasma TGF-β1 level were decreased markedly (P <0.01).The correlation analysis showed that there were significantly negative correlation between EMPs and regulatory T cells,Foxp3 mRNA expression level and TGF-β1 level (r = - 0.452,P = 0.001;r = - 0.466,P = 0.001;r = - 0.555,P = 0.000 ). Conclusion:EMPs may involve in the process of occurrence and development of ACS and plaque instability by regulating the differentiation and function of CD4+ CD25 + Foxp3 + regulatory T cells.

Effects of atorvastatin on release of endothelial microparticles and myo-cardial apoptosis in rats with acute myocardial infarction / 中国病理生理杂志

AIM: To investigate the effect of atorvastatin ( AT) on the release of endothelial microparticles (EMP) and myocardial apoptosis in the rats with myocardial infarction .METHODS: SD male rats (n=24) were ran-domly divided into 3 groups:sham operation ( sham) group , myocardial infarction ( MI) group and MI+AT group.The rat model of acute myocardial infarction was prepared by coronary artery ligation .At 2 h and 24 h after modeling , the pe-ripheral blood was collected to detect creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT).The circulating levels of EMP were measured by flow cytometry .The myocardial apoptosis was detected by terminal deoxynucleotidyl transferase -mediated dUTP nick end labeling (TUNEL) assay.RESULTS: At 2 h after modeling, the level of CK-MB was signifi-cantly increased in MI group compared with sham group , and the level of EMP and the myocardial apoptotic rate were sig-nificantly increased in MI group and MI +AT group compared with sham group .At 24 h after modeling , the level of EMP was significantly increased in MI group compared with sham group .The levels of CK-MB, cTnT, EMP and the myocardial apoptotic rate were significantly decreased in MI +AT group compared with MI group .Moreover , the level of CK-MB in MI group was significantly increased at 24 h compared with that at 2 h after modeling .The levels of CK-MB, cTnT and EMP were significantly decreased in MI +AT group at 24 h compared with those at 2 h after modeling .CONCLUSION: Ator-vastatin may reduce the level of EMP and the myocardial apoptotic rate in the rats with acute myocardial infarction , indica-ting that atorvastatin plays a role in protecting endothelium .

A comparative study of protective action on endotheliocytes of fucoidan with different molecular weight and its mechanism / 中国药学杂志

OBJECTIVE: To study the protective action on endotheliocytes of fucoidan with different molecular weight from Laminaria japonica, and to explore its mechanism. METHODS: In vivo, endotheliocytes injury model in rats was used to examine the protective action on endotheliocytes of fucoidan with different molecular weight from Laminaria japonica; aortal endothelium section by HE stain under optical microscope was observed, and the the content of von willebrand factor (vWF) in plasma was determined by ELISA. In vitro, endothelial cell culture was used to determine the effect of fucoidan on content of vWF and endothelial microparticles (EMPs). RESULTS: In vivo, aortal endothelium section by HE stain under optical microscope showed low molecular weight (LMW) fucoidan had a remarkable protective effect, and the protection effect of LMWF fucoidans are stronger than middle molecular weight (MMW) fu-coidans. Administration of LMW fucoidan significantly decreased the vWF content. Administration of MMW fucoidan didn't change vWF content. In vitro, Administration of LMW fucoidan significantly decreased the vWF content and EMPs numbers. Administration of MMW fucoidan didn't change the vWF content and EMPs numbers. CONCLUSION: The LMW fucoidan fractions have good protective action on endothelial cells. The protective effect of LMW fucoidans is significantly stronger than MMW fucoidans. The protective action on endotheliocytes of LMW fucoidans relies on decreasing the concentration of EMPs and vWF, and thus inhibiting platelet activation indirectly.

TNF-α promotes the quantity and ICAM-1 expression of endothelial microparticles / 医用生物力学

Objective To study the role of cyclic strain-modulated tumor necrosis factor-α (TNF-α) played in the quantity and intercellular cell adhesion molecule-1(ICAM-1) expression of endothelial microparticles (EMPs). Methods The endothelial cells (ECs) primarily cultured from rat aorta were applied with 5% cyclic strain (to simulate normal physiological condition) and 18% cyclic strain (to simulate hyper-tension condition), respectively, by using FX-4000T cyclic stain loading system for 24 hours at the loading frequency of 1.25 Hz. The mRNA expression of TNF-α under different amplitudes of cyclic strain was determined by real time-PCR. The TNF-α was then used to stimulate the ECs from rat aorta, and the supernatants were collected and ultracentrifuged to get endothelial microparticles (EMPs), which were then identified by lipophilic styryl membrane staining and transmission electron microscope for morphological identification. The quantities of Annexin V positive EMPs under TNF-α stimulation were counted by flow cytometer and ICAM-1 expression on EMPs was detected as well. Results Compared with the 5% normal cyclic strain, under 18% high cyclic strain condition,the mRNA expression of TNF-α in ECs increased significantly. TNF-α could then significantly up-regulate the production of Annexin V positive EMPs and promote the expression of ICAM-1 on EMPs. Conclusions The over-expression of TNF-α in ECs under high cyclic strain might mediate the high production of EMPs and over-expression of ICAM-1 on EMPs. The research findings will provide new experiment evidence for further studying the role of EPCs in the mechanobiological mechanism of vascular remodeling.

Correlation between endothelial microparticles and interleukin-6 and C-reactive protein in patients with coronary heart disease / 国际检验医学杂志

Objective To investigate alterations of endothelial microparticles(EMPs) levels in patients with coronary heart dis‐ease(CHD) ,and to evaluate the relationship between EMPs and interleukin‐6(IL‐6) and C‐reactive protein(CRP) .Methods A to‐tal of 38 patients with CHD were divided into myocardial infarction(MI) group(13 cases) and unstable angina(UA) group(13 ca‐ses) and stable angina(SA) group(12 cases) ,and 12 healthy subjects were enrolled as control group .Levels of EMPs were meas‐ured by using flow cytometry technique .Concentration of IL‐6 and CRP were determined by using enzyme linked immunosorbent assay and special protein analysis respectively .Results Compared with SA group and control group ,levels of EMPs were signifi‐cantly increased in MI group and UA group(P<0 .05) .Levels of EMPs in patients with CHD were significantly correlated with IL‐6 and CRP ,with correlation coefficient of 0 .79 and 0 .50 respectively(P<0 .05) .Conclusion EMPs could contribute to monitoring and evaluating the degree of endothelial cells injury in patients with CHD as a laboratory indicator .EMPs might enhance the vascu‐lar inflammation in patients with CHD ,and further accelerate the development of CHD .

Effect of Lipoic Acid Treatment on Endothelial Microparticles in Patients with Diabetic Peripheral Artery Disease in Lower Limbs / 医药导报

Objective To evaluate the effect of lipoic acid on endothelial microparticles (EMP) in diabetic patients with peripheral artery disease (PAD) of the lower limbs. Methods Forty eight diabetic patients with PAD of the lower limbs were randomly divided into two groups: the therapeutic group and control group (each group has 24 cases). Patients of control group only received internal comprehensive medicine therapies for 3 weeks. Patients of therapeutic group were treated with both lipoic acid (600 mg lipoic acid injection in normal saline solution for intravenous drip, once daily for 3 weeks) and internal comprehensive medicine therapies at the same time. The levels of EMP in venous blood and Ankle-brachial index (ABI) were estimated before and after treatment by flow cytometry. Results Compared to the control group after treatment [(1 179. 8± 120. 1) per μL], EMP value showed a significant reduction in therapeutic group [(1 032. 4±117. 2) per μL] (P<0. 01). The levels of ABI of therapeutic group (0. 68 ±0. 10) was increased obviously as compared that before lipoic acid treatment (P<0. 01). Patients treated with lipoic acid showed the higher levels of ABI than the control group after treatment (0. 58±0. 11) (P<0. 01). Conclusion Lipoic acid injection significantly decreased the level of EMP in diabetic patients with PAD of lower limbs. Lipoic acid might be an effective drug for diabetic patients with PAD.

Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.

Plasma Endothelial Microparticles, TNF-α and IL-6 in Kawasaki Disease.

Kawasaki disease (KD). EMPs were enumerated by flow cytometry, while IL-6 and TNF-α were measured using enzyme-linked immunosorbent assay. EMPs and IL-6 were elevated in KD, the level of TNF-α in KD was not different from disease controls, but higher than healthy controls. EMPs were positively correlated with TNF-α and negatively correlated with albumin. Elevated level of EMPs, a biomarker of endothelial cells damage, concomitant with increased levels of TNF-α and IL-6, is seen in patients with KD.

Impacts of Different Doses of Alcohol on Rat Endothelial Microparticles / 天津医药

Objective To discuss the impacts of different doses of alcohol on the level of microparticles (EMPs) of rat endothelial cells. Methods Sixty male SD rats were randomly allocated into four groups:high dose group (group A), me-dium dose group (group B), low dose group (group C) and the blank contrast group (group D). There were15 rats in each group. Rats were fed alcohol for 8 weeks. Flow cytometer was used to measure the level of circulating CD31+/CD42-EMPs in four groups, and which was compared with the alcohol dosage. Results Compared with group D, the level of circulating EMPs was significantly increased in group A and B (P＜0.05). There was no significant change in the level of circulating EMPs in group C (P>0.05). Conclusion The moderate and high doses of alcohol are harmful to the function of vascular en-dothelial cells in rats, which show a significant dose-effect relationship. The low dose of alcohol shows no effect on the func-tion of vascular endothelial cells in rats. The protective effect of alcohol needs further investigation.

The relationship between endothelial microparticles in patients with ST-elevated myocardial infarction and myocardial injury / 中华急诊医学杂志

Objective To observe the level of circulating CD31 +/CD42b-endothelial microparticles in patients with ST-elevated myocardial infarction (STEMI),and discuss the correlation between CD31 +/CD42b-and traditional myocardial injury index.Methods A total of 22 healthy subjects and 44 patients with angiographically confirmed coronary atherosclerotic lesions collected from January 2010 to December 2010 were studied prospectively.The patients were divided into SAP (stable angina pectoris,Canadian Cardiovascular Society,CCS Ⅱ to Ⅲ ) group (n =22) and STEMI group (n =22).The level of circulating CD31 +/CD42b-endothelial microparticles was detected by flow cytometric device after admission; creatine kinase (CK) and its isoenzymes (CK-MB) were detected by using biochemical analyzer; C-reactive protein was determined by a highly sensitive latex-enhanced turbidimetric immunoassay with a low detection limit of 0.25 mg/dl (IMMAGE,Beckman Coulter; Reagent from Orion Diagn Co.Ltd.,Vantaa,Finland).Cardiac troponin I was measured by chemiluminescence immunoassay (ACCESS2 from Beckman Coulter).In 22 STEMI patients,blood sample was taken not only after admission but subsequently at 4-hour intervals during the first 48 hours.Peak levels of myocardial enzymes after injury ( creatine kinase,CK; creatine kinase MB isoenzyme,CK-MB; c troponins I,cTnI) and high sensitive C reactive protein (hs-CRP) values were determined.The correlation between circulating level of CD31 +/CD42b(-) and peak levels of myocardial biomarkers after injury were analyzed.Results The endothelial micro-particles were significantly higher in STEMI patients than those in either SAP group or normal group ( P ＜ 0.01 ),whereas there was no difference between the latter two groups.In STEMI patients studied in these cross sectional study,circulating CD31 +/CD42b-microparticles were positively correlated with peak level of myocardial biomarkers after injury.Moreover,the correlations between myocardial biomarkers after injury ( CK,CK-MB,cTnl and hs-CRP) and circulating CD31 +/CD42b-microparticles were r =0.489,P =0.021; r =0.501,P=0.018; r=0.491,P=0.02; r=0.612,P=0.002.Conclusions The level of circulating blood CD31 +/CD42b-endothelial micro-particle was expected to become a predictive marker in STEMI.