Fatty acid composition of serum lipids of mothers and their babies after normal and hypertensive pregnancies

The biochemical essential fatty acid (EFA) status of neonates born after normal and hypertensive pregnancies (PIH) and that of their mothers was assessed by measuring the fatty acid composition of phospholipids (PL), triglycerides (TG) and cholesterol esters (CE) of umbilical cord serum and maternal serum, respectively. Relative contents of linoleic acid of serum PL and CE were significantly lower in mothers with PIH compared to normal pregnancies. Most other (n-6) polyenes in PL tended to be higher under hypertensive conditions. Total maternal (n-3) polyenes of serum PL were significantly higher in PIH, mainly due to clupanodonic acid, 22:5 (n-3), and cervonic acid, 22:6 (n-3). Total maternal (n-7) and (n-9) fatty acids were also significantly higher in PIH (PL and CE). The results indicate that PIH is associated with a relative increased unsaturation of maternal serum PL, which might facilitate the placental transfer of long-chain, polyunsaturated fatty acids. As a result, the neonatal EFA status after PIH only slightly differs from normal.     

Maternal BMI Associations with Maternal and Cord Blood Vitamin D Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Participants

ObjectiveObesity in pregnancy may be associated with reduced placental transfer of 25-hydroxyvitamin D (25-OHD). The objective of this study was to examine associations between maternal BMI and maternal and cord blood levels of 25-OHD in full term neonates born to a single racial cohort residing at similar latitude. Secondary objectives were to examine associations between maternal glucose tolerance with maternal levels of 25-OHD and the relationship between cord blood 25-OHD levels and neonatal size.MethodsThis study was conducted among participants of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study meeting the following criteria: residing at latitudes 41–43°, maternal white race, and gestational age 39–41 weeks. Healthy pregnant women underwent measures of height, weight, and a 75-g fasting oral glucose tolerance test (OGTT) at approximately 28 weeks gestation. Maternal and cord blood sera were analyzed for total 25-OHD by HPLC tandem mass spectrometry. Statistical analyses included ANOVA and linear regression models.ResultsMaternal and cord blood (N = 360) mean levels (sd) of 25-OHD were 37.2 (11.2) and 23.4 (9.2) ng/ml, respectively, and these levels were significantly different among the 3 field centers (ANOVA p< 0.001). Maternal serum 25-OHD was lower by 0.40 ng/ml for BMI higher by 1 kg/m² (p<0.001) in an adjusted model. Maternal fasting plasma glucose, insulin sensitivity, and presence of GDM were not associated with maternal serum 25-OHD level when adjusted for maternal BMI. Cord blood 25-OHD was lower by 0.26 ng/ml for maternal BMI higher by 1 kg/m² (p<0.004). With adjustment for maternal age, field center, birth season and maternal serum 25-OHD, the association of cord blood 25-OHD with maternal BMI was attenuated. Neither birth weight nor neonatal adiposity was significantly associated with cord blood 25-OHD levels.ConclusionThese results suggest that maternal levels of 25-OHD are associated with maternal BMI. The results also suggest that interpretation of neonatal 25-OHD levels may need to incorporate specific maternal factors in addition to season of birth and latitude.     

脐动脉血流对预测子痫前期新生儿和产妇结局的价值分析

目的:探讨应用脐动脉血流用于预测子痫前期新生儿和产妇结局的临床价值。方法:选择在我院产科建档分娩的120例孕产妇作为研究对象,根据子痫前期发病情况分为子痫前期组60例与对照组60例,记录和比较两组孕产妇的一般资料、血脂、血糖水平、分娩前脐动脉血流与新生儿体重、胎盘的重量及Apgar评分,并进行相关性与危险因素分析。结果:两组孕产妇的年龄、孕次、产次、流产次数、孕周等对比差异均无统计学意义(P0.05)。子痫前期组的血清HDL-C水平低于对照组(P0.05),血清TC、TG、LDL-C、FBG水平高于对照组(P0.05)。与对照组比较,子痫前期组脐动脉S/D、RI与PI值显著升高(P0.05)。所有孕产妇都顺利完成分娩,孕产妇与新生儿都存活,子痫前期组的新生儿出生体重及Apgar评分和胎盘的重量均显著低于对照组(P0.05)。在子痫前期组中,脐动脉S/D、RI、PI值与新生儿出生体重呈现显著负相关性(P0.05)。多重线性回归分析显示子痫前期孕产妇的脐动脉S/D、RI、PI值为影响新生儿出生体重的独立危险因素(P0.05)。结论:脐动脉血流与子痫前期新生儿出生体重显著相关,脐动脉S/D、RI、PI值为影响新生儿出生体重的独立危险因素,子痫前期脐动脉血流监测可为预测新生儿和产妇结局以及预后提供参考。     

Human serum stimulates endothelin-1 synthesis more potently than prostacyclin production by cultured vascular endothelial cells

Human serum stimulated the synthesis of a vasoconstrictive peptide, endothelin-1 (ET-1), and a vasodilatory prostanoid, prostacyclin (PGI2), by cultured human umbilical vein endothelial cells in a concentration- and time-dependent manner. Incubation in 20% concentration of the serum for 24 h stimulated ET-1 synthesis almost six-fold while PGI2 production increased two-fold. In addition, a tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), inhibited the serum-induced ET-1 production and stimulated PGI2 synthesis in a concentration- and time-dependent manner. Our results suggest that human serum derived factor(s) stimulate the production of vasoconstrictive ET-1 more potently than the synthesis of vasodilatory PGI2 by human vascular endothelial cells and that the production of these agents is differentially regulated by PMA.     

Endothelin stimulates accumulations of cellular atrial natriuretic peptide and its messenger RNA in rat cardiocytes

The effect of endothelin-1 (ET-1) on secretion and synthesis of rat atrial natriuretic peptide (rANP) as well as its mRNA levels was studied in primary cultures of neonatal rat atrial cardiocytes. ET-1 dose-dependently (10(-10)-10(-7) M) increased media and cellular rANP-like immunoreactivity as well as its cytoplasmic mRNA levels in rat cardiocytes during 24 hrs incubation. These results suggest that ET-1 directly stimulates expression of the rANP gene in cardiocytes, thereby leading to enhanced synthesis and secretion of rANP.     

Interday variation and effect of transportation on indirect blood pressure measurements, plasma endothelin-1 and serum cortisol in Standardbred and Icelandic horses

ABSTRACT: BACKGROUND: Systemic hypertension is a prominent feature in humans with metabolic syndrome (MS) and this is partly caused by an enhanced endothelin-1 (ET-1) mediated vasoconstriction. There are indications that systemic hypertension might be a feature in equine metabolic syndrome (EMS) but if ET-1 is involved in the development of hypertension in horses is not known. Increased levels of cortisol have also been found in humans with MS but there are no reports of this in horses. Before blood pressure, plasma ET-1 and serum cortisol can be evaluated in horses with EMS, it is necessary to investigate the interday variation of these parameters on clinically healthy horses. The aims of the present study were therefore to evaluate the interday variation and influence of transportation on systemic blood pressure, plasma ET-1 and serum cortisol in healthy Standardbred and Icelandic horses, and to detect potential breed differences. METHODS: Nine horses of each breed were included in the study. Blood pressure was measured and blood samples were collected between 6 and 9 am on two separate days. Eight of the horses (four of each breed) were transported to a new stable were they stayed overnight. The next morning, the sampling procedure was repeated. RESULTS: The interday variation was higher for plasma ET-1 (37%) than for indirect pressure measurements (8-21%) and serum cortisol (18%). There were no differences in systemic blood pressure between the two breeds. The Icelandic horses had significantly lower serum cortisol and significantly higher plasma ET-1 concentrations compared to the Standardbred horses. Plasma ET-1 was significantly elevated after transportation, but systemic blood pressure and serum cortisol did not differ from the values obtained in the home environment. CONCLUSIONS: Indirect blood pressure, plasma ET-1 and serum cortisol are of interest as markers for cardiovascular dysfunction in horses with EMS. The elevated plasma ET-1 concentrations recorded after transportation was likely caused by a stress response. This needs to be considered when evaluating plasma ET-1 in horses after transportation. The differences detected in plasma ET-1 and serum cortisol between the two breeds might be related to differences in genetic setup, training status as well as management conditions.     

痛风患者血管内皮功能及颈动脉粥样硬化的临床研究

目的:观察痛风患者氧化应激指标与颈动脉内膜中层厚度(IMT)的变化,探讨高尿酸引起内皮功能损伤和颈动脉粥样硬化的机制。方法:选择痛风患者123例,正常健康者116例,检测两组患者血尿酸、细胞间粘附分子1(ICAM-1)、内皮素-1(ET-1)、一氧化氮(NO)、纤溶酶原激活抑制剂-1(PAI-1)、收缩压、舒张压、空腹血糖、HDL-C、LDL-C、TC、TG等糖、脂代谢指标及颈动脉内膜中层厚度(IMT)。分析痛风患者内皮损伤相关因子水平和颈动脉IMT的关系。结果:痛风组血清细胞间粘附分子1(ICAM-1)、内皮素-1(ET-1)、纤溶酶原激活抑制剂-1(PAI-1)水平较对照组增高,颈动脉IMT明显增厚,NO水平较对照组降低,差异均有统计学意义(P0.05)。血尿酸水平、ICAM-1、ET-1、PAI-1与IMT密切相关(P0.01)。结论:痛风患者较对照组存在更明显的代谢紊乱,血管内皮功能损伤,更易发生动脉粥样硬化。     

Induction of the oxLDL receptor LOX-1 by endothelin-1 in human endothelial cells.

In this study, we analyzed the effect of endothelin-1 (ET-1) on expression of the lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 LOX-1 and on oxLDL uptake in primary cultures of human umbilical vein endothelial cells (HUVEC). LOX-1 mRNA was quantified by standard-calibrated competitive RT-PCR, LOX-1 protein expression by Western analysis and endothelial oxLDL uptake using DiI-labeled oxLDL. ET-1 induces LOX-1 mRNA expression, reaching its maximum after 1 h (160 +/- 14% of control, 100 nM ET-1, P < 0.05). This increased ET-1-mediated LOX-1 mRNA expression could be inhibited by endothelin receptor B antagonist BQ-788. In addition, ET-1 stimulates LOX-1 protein expression and oxLDL uptake in HUVEC. The augmented oxLDL uptake by ET-1 is mediated by endothelin receptor B, but not by protein kinases. These data support a new pathophysiological mechanism how locally and systemically increased ET-1 levels could promote LOX-1-mediated oxLDL uptake in human endothelial cells and the development and progression of endothelial dysfunction and atherosclerosis.     

苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病的疗效及对患儿血清HIF-1α、LXA4、ET-1表达的影响

目的:探讨苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病的疗效及对患儿血清缺氧诱导因子-1α(HIF-1α)、血脂氧素A4(LXA4)、内皮素-1(ET-1)表达的影响。方法:选择2013年1月至2018年3月我院接诊的88例缺氧缺血性脑病新生儿作为本研究对象,将其按照随机数表法分为试验组45例和对照组43例。对照组在常规治疗基础上给予脑苷肌肽注射液2 mL加入0.9%氯化钠溶液50 mL中静脉滴注,1次/d;试验组在对照组基础上给予苯巴比妥钠注射液肌肉注射,首次剂量10 mg/kg/次,24 h内可重复给药2~3次,24 h总剂量最高不超过30 mg/kg,之后以5 mg/kg/d的维持剂量,分2次使用,均连续治疗14 d。比较2组的临床疗效、临床症状恢复时间、治疗前后血清HIF-1α、LXA4、ET-1水平、神经行为评分(NBNA)、心理运动发育指数(PDI)、智力发育指数(MDI)的变化及不良反应的发生情况。结果:治疗后,试验组临床疗效总有效率为93.33%,显著高于对照组(76.74%,P<0.05),原始反射、肌肉张力、意识障碍恢复时间均明显短于对照组(P<0.05),血清HIF-1α、ET-1水平均明显低于对照组,而血清LXA4水平、NBNA评分、PDI评分、MDI评分明显高于对照组(P<0.05)。两组治疗期间均未有发热、皮疹、肝肾功能障碍等不良反应发生。结论:苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病疗效明显优于脑苷肌肽治疗,其可有效调节血清HIF-1α、LXA4、ET-1水平,促进神经功能恢复,且安全性高。     

Roles of endothelin-1 and selected proinflammatory cytokines in the pathogenesis of proliferative diabetic retinopathy: Analysis of vitreous samples

PurposeTo investigate the roles of endothelin-1(ET-1), TNF-α, IL-6 in the pathogenesis of proliferative diabetic retinopathy (PDR) in type 2 diabetes.MethodsVitreous and blood serum samples were collected during vitrectomy from 19 patients with PDR and 15 patients who underwent vitrectomy for other reasons. The concentrations of ET-1, TNF-α, IL-6, vWF, sE-selectin were determined by ELISA.ResultsIntraocular and serous concentrations of ET-1, TNF-α, IL-6, vWF, sE-selectin were higher in patients with PDR than in the control group. The vitreous ET-1/plasma ET-1 ratios the group of diabetic patients and in the control group were similar. Also TNF-α, IL-6 vitreous/plasma ratio were not statistically different between the analysed groups. Correlation between intraocular ET-1 and TNF-α concentrations in patients with PDR and between the increases in both factors in the vitreous and HbA₁c concentration were shown. In the vitreous the increase in vWF depended on elevated levels of vWF in the serum. E-selectin concentration correlated with diastolic blood pressure.ConclusionThese data provide evidence of the activation of the local synthesis of ET-1, TNF-α, IL-6 in PDR. The relationship between the increase in vitreous ET-1, TNF-α concentrations and HbA₁c concentration is a important confirmation of the necessity to optimise diabetes treatment.     

Spontaneous and stimulated interleukin-6 and tumor necrosis factor-alpha production at delivery and three months after birth

OBJECTIVE: To study the production and interrelations of maternal and neonatal cytokines (IL-6 and TNF-alpha) during labor, after vaginal delivery and at three months after delivery. METHOD: The unstimulated concentrations of cytokines in the supernatants of whole-blood cultures and concentrations after PMA (phorbol 12-myristate 13-acetate) and concanavalin (conA) stimulation were determined by enzyme-linked immunosorbent assays (ELISAs). The blood samples were from the peripheral veins of 27 healthy women during term labor and immediately after delivery and three months after delivery. Neonatal samples were taken at birth (cord blood) and three months after delivery. RESULTS: IL-6 responses to stimulation were increased in the parturients and in umbilical cord blood at delivery compared with maternal and neonatal samples obtained 3 months postpartum. In contrast, the production of maternal TNF-alpha in peripheral blood was down-regulated at delivery compared with values 3 months postpartum. After an IL-6 and TNF-alpha burst in umbilical cord samples, neonatal cytokine production was at a low level three months after delivery. IL-6 production tended to be higher in both umbilical cord blood as well as in maternal samples after delivery in women who were younger. In addition, TNF-alpha production in umbilical cord blood was significantly higher in those women who were younger. CONCLUSIONS: The production of IL-6 was up-regulated in both the maternal and in umbilical cord blood at delivery. The production of TNF-alpha was up-regulated in umbilical cord blood compared with neonatal values 3 months after birth. Maternal age had effects on IL-6 and TNF-alpha production at delivery.     

Hyperthyroidism is associated with higher plasma endothelin-1 concentrations

The objective of this study was to determine the change of plasma endothelin (ET)-1 concentrations and insulin resistance index after therapy for hyperthyroidism. We studied 20 patients with hyperthyroidism (15 women and 5 men; age, 34.0 +/- 2.8 years), and 31 patients with euthyroid goiters as controls (27 women, 4 men; age, 37.0 +/- 2.4 years). All hyperthyroid patients were treated with antithyroid drugs. The patients received evaluations before and after normalization of thyroid function. The evaluations included body mass index (BMI), body fat, and measurement of circulating concentrations of thyroid hormones, glucose, insulin, and ET-1. Hyperthyroid subjects had higher plasma ET-1 concentrations than the control group (P < 0.001). No significant differences in serum glucose and insulin concentrations or insulin resistance index estimated by the R value of the homeostasis model assessment (HOMA-R) were noted between the groups. Plasma ET-1 concentrations decreased after correction of hyperthyroidism compared with pretreatment (P = 0.006). Serum glucose concentrations decreased after correction of hyperthyroidism (P = 0.005). Moreover, both body weight-adjusted insulin concentrations and the HOMA-R index were also decreased after correction of hyperthyroidism compared with pretreatment (P = 0.026 and P = 0.019, respectively). Pearson's correlation revealed that plasma ET-1 levels positively correlated with serum triiodothyronine (T3) and free thyroxine (FT4) levels. Serum insulin levels and the HOMA-R index positively correlated with BMI and body fat. The HOMA-R index also positively correlated with serum T3 and FT4 levels. Neither insulin levels nor the HOMA-R index correlated with ET-1 levels. Hyperthyroidism is associated with higher plasma ET-1 concentrations. In addition, correction of hyperthyroidism is also associated with a decrease of plasma ET-1 levels as well as the insulin resistance index calculated by HOMA-R.     

Altered sensitivity to a novel vasoconstrictor endothelin-1 (1-31) in myometrium and umbilical artery of women with severe preeclampsia

We have suggested that a novel endothelin-1 with 31 amino acids [ET-1 (1-31)] plays an important role in fetal circulation, owing to a strong contractile activity on the umbilical artery. To clarify the pathophysiological significance of ET-1 (1-31) in the development of severe preeclampsia, its contractile activities on human umbilical arteries and uterine smooth muscle from patients with preeclampsia were studied. The contraction by ET-1 (1-31) was stronger in uterine smooth muscle of the patients with severe preeclampsia than that of normal subjects. On the contrary, the constriction of umbilical artery of the patients with eclampsia was significantly weaker than that of normal pregnant women. The stronger contraction of myometrium by ET-1 (1-31) in patients with severe preeclampsia observed for the first time in the present study suggests that ET-1 (1-31) might be involved in the development of preeclampsia.     

Obesity-induced upregulation of myocardial endothelin-1 expression is mediated by leptin

Several studies have shown that leptin, the product of the obese gene, may link obesity with cardiovascular diseases, and in particular with cardiac hypertrophy. In vitro studies suggest that the mechanism by which leptin causes cardiac hypertrophy involves the upregulation of endogenous endothelin-1 (ET-1), a potent vasoconstrictor and mitogen. Whether obesity-associated hyperleptinemia causes an increase in myocardial ET-1 expression in vivo remains unclear. To address this issue, we fed mice with a high-fat diet and analyzed serum levels of ET-1 and ET-1 mRNA in the heart. We found that in mice fed a high-fat diet, serum ET-1, myocardial ET-1, leptin and leptin receptor mRNA were all elevated. In contrast, in leptin-deficient obese (ob/ob) mice, both serum and myocardial ET-1 levels were not higher than in wild type mice. These findings suggest that upregulation of myocardial ET-1 by obesity is mediated by leptin.     

ET-3 sensitive reduction of tissue blood flow in rat liver.

Changes in gastric mucosal and hepatic tissue blood flow were simultaneously determined using a laser-Doppler blood flow meter in rats given i.v. injection of endothelin-1 (ET-1) and endothelin-3 (ET-3), both at 2 nmol/kg. Gastric mucosal blood flow decreased significantly after administration of ET-1 compared to after administration of ET-3. Decreases in blood flow due to ET-1 were reversed by pre-treatment with 10 mg/kg of BQ-123 (sodium salt), an ETA receptor antagonist, to levels comparable to those induced by ET-3, but BQ-123 had no effects on decreases in blood flow due to ET-3. On the other hand, decreases in hepatic tissue blood flow by ET-3 were significant compared to those by ET-1. Decreases in hepatic tissue blood flow due to ET-1 were slightly inhibited by pre-treatment with 10 mg/kg of BQ-123, but it had no effect at all on decreases due to ET-3. These findings indicate that decreases in gastric mucosal blood flow are mainly caused by ET-1 via ETA receptors inhibited by BQ-123, while decreases in hepatic tissue blood flow are caused mainly by ET-3 via non-ETA receptors not inhibited by BQ-123. The fact that ET-3 decreases blood flow more significantly than ET-1 suggests the involvement of ET-3 selective receptors (ETc). The findings obtained in the present study indicate that complex mechanisms are involved in the regulation of tissue blood flow by ET, with different receptor subtypes and ET family peptides being involved according to the type of tissue.     

Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1

Elevated VEGF blood concentrations have been proven to be associated with poor prognosis in human neoplasms. This finding is generally explained as a consequence of the potential angiogenic properties of VEGF itself. However, preliminary experimental studies suggest that VEGF, in addition to its angiogenic activity, may also play an immunosuppressant role by inhibiting dendritic cell (DC) maturation. The present study was performed to analyze blood levels of VEGF in cancer patients in relation to those of another potentially angiogenic tumor growth factor, endothelin-1 (ET-1), and to the absolute number of circulating immature and mature DC, and serum levels of the best known antitumor cytokine, IL-12. The study was performed in 100 healthy controls and in 80 solid tumor patients (colorectal cancer: 24; gastric cancer: 17; cancer of pancreas: 4; lung cancer: 13; breast cancer: 11; renal cell cancer: 6; gynecologic tumors: 5), 48 of whom showed distant organ metastases. In each patient, we have evaluated serum concentrations of VEGF-165, total VEGF, ET-1, IL-12 and the circulating number of immature (CD123+) and mature (CD11c+) DC. Mean serum levels of VEGF-165 were significantly higher in metastatic patients than in controls or in non-metastatic patients, whereas the total amounts of VEGF were not significantly higher. Moreover, it has been observed that patients with abnormally elevated blood concentrations of VEGF-165 showed significantly lower mean values of immature DC, mature DC and IL-12 and significantly higher mean levels of ET-1 than those with normal concentrations. This study, by confirming that advanced neoplastic disease may be associated with increased endogenous secretion of VEGF, seems to suggest that the association between high blood levels of VEGF and poor prognosis in cancer does not depend only on VEGF-induced stimulation of the neovascularization, but also on VEGF-related immunosuppression.     

妊娠高血压视网膜病变影响因素分析及血管内皮功能检测的临床意义

目的:探讨妊娠高血压视网膜病变的影响因素及血管内皮功能检测的临床意义。方法:前瞻性选取2017年1月~2018年12月期间湖北省妇幼保健院收治的150例妊娠高血压视网膜病变患者作为观察组,根据国际通用的Duker-Elder眼底分期标准分为Ⅰ期组69例,Ⅱ期组57例,Ⅲ期组24例。选取同时期该院收治的妊娠高血压无视网膜病变患者40例为对照组。采用酶联免疫吸附法检测血清胰岛素样生长因子(IGF-1)、内皮素-1(ET-1)水平,采用Pearson相关性分析IGF-1和ET-1水平与病变程度的相关性,采用多因素Logistic回归分析妊娠高血压视网膜病变的影响因素。结果:随着Duker-Elder眼底分期的增加,血清ET-1水平呈不断升高趋势,IGF-1水平呈不断下降趋势(P<0.05)。Pearson相关性分析显示,病变程度与血清IGF-1水平呈负相关,而与ET-1水平呈正相关(P<0.05)。单因素分析结果显示,妊娠高血压视网膜病变的发生与病程、孕周、血压、体质量、蛋白尿、红细胞压积有关(P<0.05),而与年龄无关(P>0.05)。Logistic回归分析结果显示,病程>3W、血压≥160/110 mm Hg、体质量>85kg、蛋白尿为+++、红细胞压积>0.35均是妊娠高血压视网膜病变发生的独立危险因素(P<0.05),而孕周>28W则是其保护因素(P<0.05)。结论:妊娠高血压视网膜病变患者存在IGF-1、ET-1的异常表达,且其表达水平与病变程度息息相关。血压、病程、蛋白尿、体质量、红细胞压积均是妊娠高血压视网膜病变发生的独立危险因素,孕周则是其保护因素。