Birth weight and its relationship with endothelial function and pattern of endothelium-derived microparticles during childhood: New insight about early vascular damage.

AIMS: To investigate whether a specific endothelium-derived microparticles (EMPs) phenotype could be associated with birth weight and microvascular endothelial function in children. MATERIALS AND METHODS: A total of 95 children aged 6-14 years were recruited. Anthropometric measurements, blood pressure measurement, microvascular endothelial function testing, and biochemical profile analyses were performed. Standardized flow cytometry methods were used to identify and quantify the circulating CD144+, CD31+/annexin V+, and CD62E+ EMPs. KEY FINDINGS: The circulating number of CD31+/annexin V+ EMPs and CD144+ EMP levels were correlated with birth weight, systolic blood pressure, microvascular endothelial function, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) level. In the multivariable logistic regression models, we identified strong evidence of a higher risk of microvascular endothelial dysfunction among children with low birth weight (LBW) and increased levels of both CD31+/annexin V+ EMPs and LDL-C; LBW and elevated LDL-C levels were independent predictors of high circulating numbers of CD31+/annexin V+ and CD144+ > 75th percentile EMPs. SIGNIFICANCE: Our data provide evidence that children with LBW values showed greater numbers of circulating CD31+/annexin V+ and CD144+ EMPs. In addition, LBW and high levels of CD31+/annexin V+ and LDL-C were significant risk factors for the presence of microvascular endothelial dysfunction.

High circulating levels of CD62E+ and CD31+/Annexin V+ endothelium-derived microparticles in children with overweight/obesity: Evidence of early vascular damage.

BACKGROUND: Obesity perturbs endothelium integrity, leading to endothelial activation, which predisposes the release of endothelium-derived microparticles (EMP). We measured the CD31+/annexin V+ and CD62E+ EMP levels to improve our understanding of their contribution to endothelial damage in children with overweight/obesity. SUBJECT AND METHODS: In this cross-sectional study, 107 children with normal weight and 35 children with overweight/obesity were evaluated. Anthropometric measurement, blood pressure, biochemical profile was performed. Standardized flow cytometry methods were used to identify and quantify circulating CD31+/annexin V+ and CD62E+ EMP. RESULTS: Children with overweight/obesity had significantly higher circulating levels of CD31+/annexin V+ (750 [600]) and CD62E+ (1400 [700]) EMP than those with normal weight (P < 0.001 for both). We found that EMP levels were positively correlated with body mass index (BMI), waist circumference, blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDLc), and triglycerides. The multivariable logistic regression model revealed that the risks of having high EMP levels (> 75th percentile) were high in children with both large waist circumference and elevated LDLc level. Receiver operating characteristic (ROC) curves demonstrated that the LDLc levels showed significantly greater discrimination than waist circumference for both CD31+/annexin V+ (P = 0.031) as CD62E+ EMPs (P = 0.041). CONCLUSIONS: Children with overweight/obesity have high circulating CD31+/annexin V+ and CD62E+ EMP levels, which may be an early sign of endothelial apoptosis and inflammatory activation in response to injury. These EMP levels were positively associated with several cardiometabolic risk factors. Our data underscore the negative influence of high-risk metabolic profiles on endothelial integrity in the early stages of childhood obesity.

Imbalance between the circulating endothelium-derived apoptotic microparticles and the endothelial colony-forming units of progenitor cells in patients undergoing diagnostic coronary angiography.

PURPOSE: The involvement of the circulating endothelium-derived microparticles (EMPs) and the endothelial progenitor cells (EPCs) has been shown in the pathogenesis of coronary artery disease (CAD). The current study aimed to explore whether the Friesinger index is associated with the levels of the apoptotic CD144+/CD31+/annexin V+ â€‹EMPs and the number of endothelial colony-forming units of progenitor cells in patients undergoing coronary angiography. PATIENTS AND METHODS: Fifty-seven patients with a median age of 62 years (range: 48-84 years) were enrolled. Quantification of the apoptotic CD144+/CD31+/annexin V+ EMPs was performed by flow cytometry. The number of endothelial colony-forming units defined by CFU-Hill was assessed by cell culture. RESULTS: There was a positive correlation between the Friesinger index and the circulating levels of the apoptotic CD144+/CD31+/annexin V+ EMPs (rho=0.817, p<0.001), whereas a negative correlation was found with the number of CFU-Hill (rho â€‹= â€‹- 0.649, p<0.001). Multivariable logistic analysis showed that the risk of having moderate/severe CAD was five times greater among male patients (OR:5.32; 95% CI: 1.19 - 16.33; p=0.038) and almost one and a half times higher among those with a higher level of apoptotic CD144+/CD31+/annexin V+ EMPs (OR:1.74; 95% CI: 1.23 - 2.28; p=0.001). Finally, the circulating levels of apoptotic EMPs labelled for CD144+/CD31+/annexin V+ presented a good discrimination of moderate/severe CAD, with an AUC of 0.85 (95% CI â€‹= â€‹0.74 - 0.96; p< 0.001). CONCLUSIONS: Moderate or severe CAD is associated with increased levels of apoptotic EMPs and reduced EPC colony-forming capacity, increasing the occurrence of endothelial injuries.

Elevated Microparticles, Thrombin-antithrombin and VEGF Levels in Colorectal Cancer Patients Undergoing Chemotherapy.

Hypercoagulable state and neoangiogenesis are common phenomena associated with malignancy. Cancer patients have increased levels of circulating endothelium-derived microparticles (EMPs), which have been hypothesized to be involved in numerous pathophysiological processes. Hemostasis and angiogenesis are also activated in colorectal cancer (CRC) patients. The study aimed to investigate potential influence of chemotherapy on EMPs, thrombin anti-thrombin complex (TAT) and vascular endothelial growth factor (VEGF) levels in CRC patients undergoing chemotherapy. The study group consisted of 18 CRC patients: 8 stage III colon cancer (CC) and 10 stage IV rectal cancer (RC) patients. EMPs, TAT and VEGF levels were assessed before chemotherapy and after the third course. Results were compared with 10 healthy subjects. EMP concentration was measured by flow cytometry, while TAT and VEGF concentrations were assayed employing ELISA. Compared to the control group, CC and RC patients had significantly higher levels of tissue factor (TF)-bearing and non-TF-bearing EMPs before and after three courses of chemotherapy. VEGF concentrations in CRC patients were higher than in the control groups and increased following chemotherapy. TAT levels were elevated in CRC patients before chemotherapy compared to healthy subjects and significantly increased after the third course of chemotherapy. No significant correlation was found either between EMP and TAT levels, or between EMP concentrations and VEGF levels in the study group. CRC patients have increased EMPs, and TAT as well as VEGF levels tend to increase during chemotherapy.

Cell-Derived Microparticles and Acute Coronary Syndromes: Is there a Predictive Role for Microparticles?

BACKGROUND: Despite the recent advances in the treatment of Acute Coronary Syndromes (ACS), patients with ACS are still exposed to an increased risk for adverse cardiovascular events, while their prognosis is difficult to determine. Experimental and clinical studies have shown that cell-derived Microparticles (MPs) are associated with the underlying pathophysiological processes that are responsible for atherogenesis and may be causally implicated in the induction of atherothrombosis. OBJECTIVE: In the present article, we aimed to review the available evidence regarding the predictive role of MPs in patients with ACS. RESULTS: Evidence suggests that endothelial MPs are associated with future adverse cardiovascular events in patients with ACS. Platelet-derived MPs have been excessively studied, since they have been found to trigger the coagulation cascade; however, their role as predictors of future cardiovascular events remains debatable. The role of red blood cell-derived MPs is more intriguing; they have been proposed as markers of ongoing thrombosis in patients with ACS, while previous studies have shown that they have anti-coagulant properties in healthy individuals. Leukocyte-derived MPs may also have a predictive role, although the studies regarding these are still limited. Last but not least, it was an interesting discovery that circulating MPs can provide information regarding the angiographic lesions in patients with ACS. CONCLUSION: The concept of MPs as potential circulating biomarkers in patients with ACS holds much promise. However, large-scale clinical studies are required to evaluate whether the measurement of plasma MPs could be of clinical significance and, thus, dictate a more aggressive treatment strategy in patients with high levels of circulating MPs.

Endothelium-derived microparticles induce endothelial cell superoxide generation and impair endothelial function / 中国病理生理杂志

AIM:To investigate the mechanism of endothelium-derived microparticles(EMP)-induced endothelial dysfunction and the role of superoxide anion(O-?2) in EMP-induced endothelial dysfunction.METHODS:EMP were isolated from human umbilical vein endothelial cells stimulated with plasminogen activated inhibitor-1.(1) Cultured bovine aortic endothelial cells(BAEC) were divided into 3 groups and pretreated with nothing in group 1,EMP(1?108/L) in group 2,EMP(1?108/L) + L-nitroarginiemethylester(L-NAME,1 mmol/L) in group 3 for 30 min and A23187(5 ?mol/L) stimulated O-?2 generation was determined by superoxide dismutase(SOD)-inhibitable ferricytochrome C reduction.(2) Facialis arteries(60-150 microns) were isolated from C57BL/6 mice and divided into 4 groups.The vessels were pretreated with nothing in group 1,EMP(1?108/L) in group 2,EMP(1?108/L) + SOD(2?105 U/L) in group 3,EMP(1?108/L) + polyethylene glycolated-SOD(PEG-SOD,2?105 U/L) in group 4 for 10 min and acetylcholine(ACH)-induced vasodilation was measured.RESULTS:(1) EMP significantly increased O-?2 generation in BAEC culture,which was prevented about 50% by pretreating the BAEC with L-NAME.(2) EMP significantly impaired ACH-induced vasodilation.SOD could not restore EMP-impaired ACH-induced vasodilation and PEG-SOD showed partial restoration of vasodilation.CONCLUSION:These data indicate that at least some EMP-induced endothelial dysfunction occurs by inducing intracellular O-?2 generation.It may provide a theoretical evidences in finding a multiple treatment including removal of O-?2 in the future.