Serum Levels Of Endothelin-1 Research Articles

The role of markers of endothelial dysfunction in the pathogenesis of coronary microvascular dysfunction in patients with non-obstructive coronary artery disease

Aim. To study the potential of non-invasive biomarkers in the diagnosis of coronary microvascular dysfunction (CMD) and prediction of the course of heart failure with preserved ejection fraction (HFpEF) in non-obstructive coronary artery disease.Materials and methods. The 12-month observational study included 118 consecutive patients (6 patients dropped out of the study due to contact loss) with non-obstructive coronary artery disease (CAD) and HFpEF (62 [59; 64]%). At the beginning of the study, serum levels of several biomarkers were assessed using the enzyme immunoassay: N-terminal pro-B-type natriuretic peptide (NT-proBNP), vascular endothelial growth factor (VEGF), and endothelin-1. Coronary flow reserve (CFR) was examined using dynamic single photon emission computed tomography. In the absence of obstructive CAD, CMD was defined as a global decrease in CFR ≤ 2. Echocardiography was used to determine parameters of hemodynamics, LV diastolic dysfunction, and myocardial stress. LV global longitudinal strain (GLS) was assessed using 2D speckle tracking.Results. The patients were divided into groups depending on the presence of CMD: group 1 included patients with CMD (n = 43), group 2 included those without it (n = 75). In patients in group 1, serum levels of endothelin-1 were 1.9 times higher (p = 0.012), levels of VEGF were 2.16 times higher (p = 0.008), and the concentration of NT-proBNP was 2.6 times higher (p = 0.004) than in patients in group 2. According to the ROC analysis, the concentrations of endothelin-1 ≥ 6.9 pg / ml (AUC = 0.711; p = 0.040) and VEGF ≥ 346.7 pg / ml (AUC = 0.756; p = 0.002) were considered as markers associated with the presence of CMD in patients with non-obstructive CAD. The multivariate regression analysis showed that only the presence of CMD (odds ratio (OR) 2.42; 95% confidence interval (95% CI) 1.26–5.85; p < 0.001) and an increase in NT-proBNP ≥ 760.5 pg / ml (OR 1.33; 95% CI 1.08–3.19; p = 0.023) were factors associated with adverse events, and their combination increased the risk of HFpEF progression by more than 3 times (OR 3.18; 95% CI 2.76–7.98; p < 0.001), whereas markers of endothelial dysfunction were not independent predictors. Conclusion. Endothelin-1 ≥ 6.9 pg / ml and VEGF ≥ 346.7 pg / ml can be used as non-invasive markers for the diagnosis of CMD. However, markers of endothelial dysfunction were not independent predictors of HFpEF progression in patients with non-obstructive CAD during 12-month follow-up.

Effects of thiacloprid, a neonicotinoid pesticide, on rat reproductive system: Pregnancy hormone disruption and abortion trends

Thiacloprid (TCL), commonly known as Biscaya, is among the most widely used pesticides in agriculture, designed to eliminate insects by targeting their nicotinic receptors. This study explores the effects of orally administering TCL (at a dose of 50 mg/kg) on the hormone secretion crucial for pregnancy and the factors influencing abortion throughout the early, middle, and late stages of pregnancy in female rats.Following TCL exposure, there were significant increases in levels of 17β-Estradiol, prostaglandins F2α and E2, and serum oxytocin hormone in different stages of pregnancy. In contrast, progesterone and endothelin-1 serum levels notably decreased during the initial and final stages of pregnancy. Additionally, TCL led to a substantial rise in lipid peroxidation levels and a decrease in total thiol molecules and total antioxidant capacity, especially in uterine tissue. Although TCL did not significantly affect the morphological characteristics of the delivered fetuses, it notably increased the number of abortions, especially during the second and third stages of pregnancy.In summary, our findings suggest that TCL elevates the risk of abortion in pregnant rats by disrupting the secretion of hormones crucial for fertility (such as 17β-Estradiol/progesterone) and by increasing the secretion of abortion-inducing hormones like prostaglandins and oxytocin. Furthermore, these effects may be associated with disruptions in the oxidant/antioxidant balance within the ovaries and uterus.

Research on the Improvement of Endothelial Cell Function and Trophoblast Apoptosis in Rats with Preeclampsia by Tanshinone IIA

Background Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, often the kidneys. Recent studies suggest that endothelial dysfunction and trophoblast apoptosis are involved in the pathogenesis of preeclampsia. Purpose To investigate the effects of tanshinone IIA (TIIA) on clinical symptoms, vascular endothelial function, and placental trophoblast apoptosis in preeclampsia rats. Materials and Methods Twenty-four pregnant Sprague-Dawley rats, between 8 and 10 weeks old, were randomly divided and allocated into three groups: Control, model, and treatment, with each group consisting of 8 rats. The control group received normal saline injections via the tail vein; the model group received NG-nitro-l-arginine methyl ester (l-NAME) to induce preeclampsia, followed by normal saline injections; and the treatment group received TIIA (10 mg/kg) via tail vein injection after preeclampsia induction with l-NAME. Various parameters were measured, including tail artery systolic pressure, 24-hour proteinuria, offspring and placental weight, levels of endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), placental growth factor (PLGF), and soluble FMS-like tyrosine kinase 1 (sFlt-1) in serum, and expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) in placental trophoblasts. Results TIIA treatment led to decreased tail artery systolic pressure and 24-hour urine protein levels, increased body and placental weights of offspring, and favorable changes in serum levels of ET-1, sFlt-1, eNOS, and PLGF. Moreover, TIIA treatment resulted in decreased Bax levels and apoptosis in placental trophoblasts, along with increased Bcl-2 levels. Conclusion TIIA can improve the clinical symptoms of preeclampsia in rats induced by l-NAME, alleviate the apoptosis of placental trophoblast cells, and improve vascular endothelial function.

Effects of acupuncture on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats

To observe the effects of acupuncture at "antihypertensive acupoint prescription" on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats, and explore the vascular regulation and central regulation mechanisms of acupuncture for anti-hypertension. Thirty SPF grade male spontaneous hypertension rats were randomly divided into a model group (15 rats) and an acupuncture group (15 rats). Besides, 15 Wistar Kyoto rats were collected as a blank control group (normal group). In the acupuncture group, acupuncture was delivered at the "antihypertensive acupoint prescription" (bilateral "Renying" [ST 9], "Quchi" [LI 11], "Zusanli" [ST 36], "Taichong" [LR 3] and "Neiguan" [PC 6]), with needles retained for 30 min, once daily. The duration of intervention was 28 days. Every week, using the the irritation scale, the sign of sympathetic irritation was evaluated dynamically. The arterial blood pressure of the rats tail was determined, using non-invasive blood pressure measurement system. ELISA was adopted to detect the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), endothelin-1 (ET-1), neuropeptide Y (NPY) in the serum. DAB chromogenic in situ hybridization (CISH) was provided to detect the mRNA expression of endothelial nitric oxide synthase (eNOS) in the internal carotid artery and the arcuate nucleus (ARC), and that of CGRP in the paraventricular nucleus posterior (PVP) and the ventrolateral medulla (VLM). Liquid chromatography-mass spectrometry (LC-MS) was used to detect the levels of epinephrine (E) and norepinephrine (NE) in the paraventricular nucleus anterior (PVA). Compared with the normal group, the irritation scores, systolic blood pressure and diastolic blood pressure were increased at each time point in the model group (P<0.05). When compared with the model group, the irritation scores after the intervention for 3 and 4 weeks, and systolic and diastolic blood pressure after intervention for 2, 3 and 4 weeks were reduced in the acupuncture group (P<0.05). In comparison with the normal group, the serum CGRP and NO levels of the rats were decreased (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels in PVA were increased (P<0.05) in the model group. The levels of serum CGRP and NO were elevated (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels of PVA were reduced (P<0.05) in the acupuncture group when compared with those of the model group. In the model group, the media of internal carotid artery exhibited thickening and remodeling, while the neuron volume in ARC was small. In the acupuncture group, every layer of internal carotid artery was acceptably arranged, and the parvicellular neuron of ARC was moderate in volume. For the in situ hybridization of eNOS mRNA for the rats of each group, the smooth muscle cells were predominantly expressed in each layer of the internal carotid artery, whereas the expression of parvicellular neurons was dominated in ARC. In the model group, the large and small neurosecretory cells were distributed sparsely in the nerves of PVP; in the acupuncture group, the cells of these two species were distributed regularly; and there were few species of glial cell in the VLM of either the model group or the acupuncture group. In each group, for the in situ hybridization of CGRP mRNA, the small neurosecretory cells were expressed predominately in the PVP, while, the expression of glial cell nuclei and the cell cytoplasm was dominated in the VLM. Compared with the normal group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP mRNA in the PVP and VLM was decreased in the model group (P<0.05). In the acupuncture group, when compared with the model group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP in the PVP and VLM was increased in the acupuncture group (P<0.05). Acupuncture at "antihypertensive acupoint prescription" can upregulate the level of vascular relaxing factors, downregulate the level of contracting factors, enhance the response of relaxing factors in targeting blood vessels and regulating the center. The mechanism may be related to the modulation of the sympathetic-adrenergic autonomic neurotransmitters in the paraventricular nucleus in spontaneous hypertension rats.

The Antihypertensive Potential of Aqueous extract of Peristrophe Bivalvis (L.) Merr. is via Up-regulation of Cyclic Guanosine Monophosphate and Down-regulation of the Renin-angiotensin System.

Hypertension is a major risk factor for cardiovascular diseases. Peristrophe bivalvis (PB) is used for the treatment of hypertension, painful sprains, skin diseases, tuberculosis, acute bronchitis, anti-inflammatory conditions, hepatitis, and diabetes. Its antihypertensive potential has been investigated and documented. This study investigated the antihypertensive mechanism of aqueous extract of PB leaf (APB) on L-NAME-induced hypertension. Thirty male wistar rats (150-170 g) were grouped into five (n=5). Group 1 received 10 mL/kg of distilled water (control), while groups 2-5 were administered 60 mg/kg of L-NAME (L-- NAME60) orally for eight weeks to induce hypertension. After eight weeks, groups 2-5 received L-NAME60+distilled water (HNT), distilled water (HRE), L-NAME60+APB (200 mg/kg, [HAPB]), and L-NAME60+ramipril (10 mg/kg, [HRA]), respectively, for five weeks. The BP was measured by the tail-cuff method. The blood sample was obtained under anesthesia, and tissue samples were obtained after euthanasia. Serum renin, ACE, angiotensin-II, endothelin-1, and cyclic guanosine monophosphate (cGMP) levels were measured using ELISA techniques. Malondialdehyde, superoxide dismutase (SOD), and reduced glutathione (GSH) levels were measured by spectrophotometry. Data were analyzed using ANOVA at α0.05. The BP significantly decreased in HAPB compared to HNT. Renin, ACE, and angiotensin-II levels significantly decreased while cGMP levels increased in the HAPB group compared to HNT. Malondialdehyde levels significantly decreased, and SOD and GSH levels increased compared to HNT. Peristrophe bivalvis aqueous leaf extract reduced blood pressure in hypertensive rats by modulating the cGMP signalling pathway and the renin-angiotensin system.

Blood serum biomarkers in the dynamics of treatment for cerebrovascular pathology in post-COVID-19 patients

Neurological manifestations after COVID-19 infections can be attributed to chronic immune and inflammatory reactions induced by SARS-CoV-2, as well as endothelial dysfunction and other vascular issues. This study included 24 patients with cerebrovascular disease (CVD) who had contracted COVID-19 1 &amp;ndash; 1.5 years before the examination (experimental group) and 20 patients with CVD who had not previously been infected with the coronavirus (comparison group). Both groups were representative in terms of age and gender. Blood serum biomarkers, including interleukin (IL)-6, endothelin-1 (ET-1), and vascular endothelial growth factor A (VEGF-A), were tested before and after a 14-day standard complex therapy in the hospital at our institute using appropriate enzyme-linked immunosorbent assay reagent kits. Increases in the levels of IL-6 (by 20%), ET-1 (by 200%), and VEGF-A (by 100%) were observed in patients with CVD who had contracted COVID-19 1 &amp;ndash; 1.5 years earlier compared to the comparison group. The effectiveness of a 2-week therapeutic intervention in patients with a history of COVID-19 was found only for VEGF-A: its serum level decreased twofold, leading to the normalization of this indicator. The concentrations of IL-6 and ET-1 were not affected by the treatment. In addition, the serum levels of ET-1 and VEGF-A in unvaccinated individuals exceeded those in vaccinated patients.

#220 Acute vascular response to hemodialysis as measured by serum syndecan-1 and endothelin-1 levels, as well as vascular stiffness

Abstract Background and Aims End-stage kidney disease (ESKD) patients on chronic hemodialysis (HD) have very high cardiovascular risk. Acute vascular changes during dialysis mediated partially by factors of the endothelium may have a crucial role in the cardiovascular (CV) disease of HD patients. Aim To study acute vascular changes during HD measured by applanation tonometry and to assess the role of syndecan-1 (SDC-1), endothelin-1 (ET-1), and traditional and non-traditional CV risk factors in these changes. Method 29 consecutive chronic HD patients (median age: 65.6 ± 10.4 years; 52% men) were included in the study. Pre-, mid-, and post-HD plasma SDC-1 and ET-1 levels and routine biochemical parameters were measured. Applanation tonometry (SphygmoCor, AtCor Medical) was performed before HD. Results As assessed by trend analysis, SDC-1 levels increased significantly during HD (p = 0.004). ET-1 levels were decreasing during HD. Male patients had significantly higher ET-1 levels than women. Patients were divided into 2 groups based on their pulse wave velocity (PWV): PWV ≥12 m/s and PWV &amp;lt;12 m/s. Pre-HD and mid-HD SDC-1 levels were significantly higher in the group with PWV ≥12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/ml, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/ml, p = 0.044, respectively). Post-HD ET-1 levels were significantly higher in the patient group having PWV ≥12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients having PWV ≥12 m/s had significantly higher pre-HD peripheral and aortic systolic blood pressure than the patients having lower PWV (147.4 ± 73.3 vs. 134.1 ± 72.2 mmHg, p = 0.038, and 130.7 ± 16.6 vs. 122.5 ± 14.9 mmHg, p = 0.016, respectively). Mid-HD and post-HD blood pressures were not different. We found a positive correlation between total cholesterol and the decrease in SDC-1 levels during HD (r = 0.539; p = 0.008). Pre-, mid-, and post-HD SDC-1 correlated significantly with the ultrafiltration volume during HD (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). Conclusion SDC-1 and ET-1 may contribute to the vascular changes observed during HD, and they have correlations with some traditional and non-traditional CV risk factors.

Effect of Intrathecal Eugenol on Cerebral Vasospasm in an Experimental Subarachnoid Hemorrhage Model

Eugenol has various curative properties. It affects the dilatation of cerebral arteries through voltage-dependent Ca2+ channel inhibition. This study is the first to explore the impact of eugenol on neuroprotection and vasospasm in an experimental subarachnoid hemorrhage (SAH) model. Twenty-four adult male Sprague-Dawley rats were indiscriminately separated into 3 groups: the control group (n=8), the SAH group (n=8), and the eugenol group (n=8). A double-bleeding method was used. The eugenol group received intracisternal eugenol (Sigma-Aldrich, St. Louis, MO, USA) at 30μg/20μl after induction of SAH. On the day 7, all groups were euthanized. Measurements were taken for basilar artery wall thickness, lumen diameter, serum endothelin-1 (ET-1), and caspase-3 levels. The eugenol group exhibited significantly lower wall thickness, ET-1, oxidative stress index, and caspase-3 levels compared to the SAH group. In comparison to the control group, the eugenol group showed a higher oxidative stress index along with higher ET-1 and caspase-3 levels, but these differences were not statistically significant. Wall thickness was significantly higher in the eugenol group than in the control group. This study represents the first literature exploration of intrathecal eugenol's impact on vasospasm induced after experimental SAH. Administration of intrathecal eugenol demonstrates a positive effect on the treatment of experimental vasospasm as well as on the reduction of oxidative stress and apoptosis.

Impact of Forced Swimming Stress on Serum Adiponectin and Endothelin-1 Levels in Wistar Rats: Comparative Analysis of Dietary Effects.

Aim This study aimed to assess the impact of forced repeated swimming stress on serum adiponectin and endothelin-1 levels in Wistar rats, comparing the effects between those fed a standard diet and those on a high-fat diet. Methods Twenty adult male Wistar rats were divided into two dietary groups: a standard food diet group (NFD, n=10) and a high-fat diet group (HFD, n=10). Both groups underwent daily forced swimming stress for six days, with durations increasing from 5 to 30 minutes. The protocol finished in an acute bout of swimming exercise on the seventh day with a duration of 40 minutes. Adherence to ethical guidelines was strictly maintained, and serum adiponectin and endothelin-1 levels were measured pre- and post-exercise using the ELISA method. Results Before swimming, the mean adiponectin levels were 4.30±1.50 ng/mL in the NFD group and 3.53±0.70 ng/mL in the HFD group. Post-exercise, these levels significantly decreased to 2.4±0.84 ng/mL (p=0.003) and 1.58±0.23 ng/mL (p=0.001), respectively. Endothelin-1 levels also showed significant decreases from 0.86 pg/mL (0.74-0.87) to 0.49 pg/mL (0.43-0.62) (p=0.003) in the NFD group, and from 0.89 pg/mL (0.86-0.93) to 0.69 pg/mL (0.60-0.75) (p=0.027) in the HFD group after swimming. Conclusion The study highlighted the significant effects of forced swimming stress on lowering serum adiponectin and endothelin-1 levels in Wistar rats, with more pronounced decreases observed in rats on a high-fat diet. The results of the study suggest the potential of exercise as a crucial component of strategies aimed at managing obesity and improving cardiovascular health, emphasizing the interaction between physical stress and dietary factors on metabolic and cardiovascular biomarkers.

Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model.

Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.

The association between endothelial function and autoimmune thyroiditis induced by iodine excess

BackgroundIodine excess (IE) intake leads to lymphocyte dysfunction and contributes to autoimmune thyroiditis (AIT). Abnormal thyroid function is associated with adverse cardiovascular events, endothelial dysfunction is often an early pathophysiological feature in most cardiovascular disease. However, the relationship between iodine and the cardiovascular system is currently unclear. Therefore, the aim of this study was to investigate the effects of IE on endothelial function in mouse model. MethodsA total of 24 NOD.H-2h4 mice were randomly divided into different groups. A sodium iodide (NaI) group supplied with 0.05% NaI water for 8 weeks. Serum levels of tumor necrosis factors α (TNFα), interleukin-6 (IL-6) and C-reactive Protein (CRP), as well as endothelin-1 (ET-1), von Willebrand factor (VWF) and thrombomodulin (THBD) were detected by Elisa. In addition, the mRNA and protein expression of these genes were measured by RT-PCR and Western blotting. ResultsHere, we found the urinary iodine concentration (UIC) was higher in the NaI group compared to the control group. Serum levels of ET-1, VWF, and THBD were also significantly lower in the NaI group, however, CRP serum levels are significantly increased. In aorta, the mRNA and protein expression of ET-1, VWF, THBD were downregulated, however, the expression of IL-6, CRP and TNFα mRNA and protein were upregulated in the NaI group. A correlation analysis showed negative correlation between UIC with ET-1, VWF, and THBD, similarly, negative correlation between CRP with THBD was observed. In addition, positive correlations between UIC with CRP. ConclusionCollectively, in the NOD.H-2h4 mice, IE supplementation had a suppressive effect on endothelial function, and this inhibition maybe due to the increase expression of inflammatory cytokines.

Can Endothelin-1 Levels in Patients with Esophageal Variceal Bleeding at Admission Predict Rebleeding Within 5 Days?

Portal hypertension complicating liver cirrhosis is associated with vascular resistance, possibly due to overexpression of humoral vasoconstrictors, including endothelin. The study aimed to evaluate the efficacy of serum endothelin-1 levels as a noninvasive predictor of early esophageal rebleeding (within 5 days) following endoscopic treatment. Of the patients presented to the endoscopy unit at Mansoura University Hospital, 50 patients were chosen for this study on the basis of endoscopically proven acute esophageal variceal bleeding consequent to hepatitis C viral infection complicated by liver cirrhosis and portal hypertension. Routine laboratory parameters and serum endothelin-1 levels were assessed prior to endoscopic treatment. Patients were divided into 2 groups depending on the development of early postendoscopic rebleeding. Group A consisted of 16 patients who developed rebleeding, while group B included 34 patients who did not. Statistical analysis was performed to determine the predictors of rebleeding. Multivariate logistic regression demonstrated that endothelin-1 level (P < .001) and serum albumin level (P = .04) were independent risk factors for early rebleeding. The most efficient cutoff value for endothelin-1 levels in predicting variceal rebleeding within the 5 days after endoscopic intervention was 65.29, which had an 88.2% specificity, 87.5% sensitivity, 88% accuracy, and area under the curve value of 0.89. In addition, hemoglobin, albumin, and creatinine levels were significantly different between bleeding and nonrebleeding groups (P = .03, P = .014, and P <.001, respectively), as was the duration of hospital stay (P < .001). Serum endothelin-1 levels appear to be a reliable, practical, noninvasive predictor of early variceal rebleeding and related comorbidities such as the severity of kidney affection and duration of hospital stay.

Mechanisms of Xuefu Zhuyu Tang in the Treatment of Diabetic Erectile Dysfunction in Rats Through the Regulation of Vascular Endothelial Function by CaSR/PLC/PKC and MEK/ERK/RSK Pathways.

Xuefu zhuyu Tang (XFZYT) is a classic formula used for promoting blood circulation and resolving blood stasis in Traditional Chinese Medicine. Clinical data have indicated that XFZYT plays a significant therapeutic role in diabetes-induced erectile dysfunction (DIED) disease, but the underlying mechanism remains elusive. Male Sprague-Dawley (SD) rats were randomly categorized into normal, model, and treatment groups. The diabetic rat model was established via intraperitoneal injection of streptozotocin. DIED rats were screened using apomorphine, and the number of erections was measured after 8 weeks of XFZYT treatment. Serum nitric oxide (NO) and endothelin-1 levels as well as penile tissue structure alterations were assessed by hematoxylin-eosin staining and electron microscopy. CaSR/PLC/PKC and MEK/ERK/RSK pathway-related proteins in the penile tissue were detected by western blotting (WB) analysis and polymerase chain reaction (PCR). Compared with the blank group, the model group rats showed a significant decrease in weight and erectile function. The pathological damage in the penile tissues of the model rats was indicated by a significantly decreased serum NO level and an increased endothelin-1 content. After treatment with XFZYT, the protein expression of CaSR, PLCβ1, PKCβ, MEK1, ERK1, and RSK1 in the penile tissue was significantly increased. Overall, the treatment group showed significant improvements in the evaluated indexes. In conclusion, this study revealed that XFZYT improves erectile function in diabetic rats, and the underlying mechanism might be linked with the regulation of CaSR/PLC/PKC and related molecules of the MEK/ERK/RSK pathway, which promotes the vascular endothelial diastolic effect.

Relationship between serum endothelin-1 and in-stent restenosis following vertebral artery stenting

The study objective was to investigate the relations between serum endothelin-1 and in-stent restenosis in vertebral artery stenting. Sixty-eight patients undergoing re-examination of vertebral artery stenting in the Department of Cerebrovascular Disease, Hangzhou Third People’s Hospital, between April 2019 and October 2022, were invited to participate. According to the presence of vertebral artery stenting, patients were divided into the restenosis (n = 19) or non-restenosis (n = 49) groups. General clinical data and endothelin-1 levels were compared between the groups. Logistic regression analysis was used to explore the relations between endothelin-1 level and risk for in-stent restenosis. Receiver operating characteristic curves were drawn to test the diagnostic value of serum endothelin-1 level for in-stent restenosis. Compared with the non-restenosis group, restenosis group levels of low-density lipoprotein, triglycerides, and endothelin-1 were significantly higher (p < 0.05) Multivariate logistic regression analysis showed that endothelin-1, stent length, and low-density lipoprotein were independently associated with in-stent restenosis (odds ratio = 1.502, 95% confidence interval: 0.042 ~ 0.212, p = 0.000; odds ratio = 1.899, 95% confidence interval: 1.116 ~ 2.237, p = 0.000; odds ratio = 1.899, 95% confidence interval: 1.228 ~ 3.337, p = 0.001, respectively). Area under the curve for serum endothelin-1 in the diagnosis of vertebral artery in-stent restenosis was 0.938. The best diagnostic cut-off value was 11.94 ng/L. Sensitivity was 89.5%. Specificity was 85.7%. These cumulative data indicate that endothelin-1 level is independently associated with in-stent restenosis.

Association between endothelin-1, nitric oxide, and Gensini score in chronic coronary syndrome

BackgroundChronic coronary syndrome (CCS) is a major public health burden; its pathogenesis involves atherosclerosis and endothelial dysfunction. Endothelin-1 (ET-1) and nitric oxide (NO) are vasoactive substances synthesized by endothelial cells that play a crucial role in CCS development. The Gensini score (GS) is used for evaluating CCS severity based on lumen segment changes, stenosis degree, and coronary stenosis site.MethodsThis prospective study included 71 patients with CCS; we evaluated the relationships between GS and ET-1 and NO serum levels were evaluated in these patients. The GS was calculated for all patients. Serum ET-1 & NO levels among other laboratory parameters were measured.ResultsThe high GS group had higher ET-1 and relatively NO expressions in the than the low GS group. GS was positively correlated with ET-1 and negatively correlated with NO, T4, and TSH levels. The results of the multiple linear regression analysis showed that ET-1 had the most significant effect on GS.ConclusionsWe found a strong association between ET-1, NO, and CCS severity. A combination of ET-1, NO, and GS is an essential predictor of CCS disease severity.

Acute Vascular Response to Hemodialysis as Measured by Serum Syndecan-1 and Endothelin-1 Levels as Well as Vascular Stiffness

Background: Chronic hemodialysis (HD) patients have a very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. The aim of this article is to study the acute vascular changes during HD. Methods: In 29 consecutive chronic HD patients (age: 65.6 ± 10.4 years), their pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. Results: Their SDC-1 levels increased during HD (p = 0.004). Males had higher ET-1 levels. The patients were divided into two groups based on their pre-HD pulse wave velocity (PWV): PWV ≥ 12 m/s and PWV &lt; 12 m/s. The pre-HD and mid-HD SDC-1 levels were higher in the group with a PWV ≥ 12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/mL, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/mL, p = 0.044, respectively). The post-HD ET-1 levels were higher in the patient group with a PWV ≥ 12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients with a PWV ≥ 12 m/s had higher pre-HD peripheral and aortic systolic blood pressures (p &lt; 0.05). The total cholesterol correlated with the SDC-1 decrease during HD (r = 0.539; p = 0.008). The pre-, mid-, and post-HD SDC-1 correlated with ultrafiltration (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). Conclusion: SDC-1 and ET-1 contribute to the vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

Hemorrhagic Fever with Renal Syndrome Patients Exhibit Increased Levels of Lipocalin-2, Endothelin-1 and NT-proBNP.

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by viruses of the Orthohantavirus genus. This syndrome is characterized by renal and cardiopulmonary implications detectable with different biomarkers. Here, we explored the role of serum and urine levels of lipocalin-2, endothelin-1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFRS pathology. A total of twenty-eight patients hospitalized due to a Puumala orthohantavirus infection were included, with serum and urine samples collected on patient admission (acute phase) and discharge (convalescent phase). In comparison to healthy individuals, patients exhibited significantly higher acute-phase serum and urine levels of lipocalin-2, serum levels of endothelin-1 and serum and urine levels of NT-proBNP. Patients in the convalescent phase showed a significant decrease in urine lipocalin-2, serum endothelin-1 and serum and urine NT-proBNP levels. We recorded a strong correlation between serum levels of lipocalin-2 and endothelin-1 and urine levels of lipocalin-2 with several kidney injury markers, such as serum creatinine, urea, urine white blood cell count and proteinuria. We also demonstrated an independent correlation of serum and urine lipocalin-2 levels with acute kidney injury in HFRS. All in all, our results show an involvement of NT-proBNP, lipocalin-2 and endothelin-1 in the renal and cardiac pathology of HFRS.

Abstract 11964: The Effect of Endothelin-1 on Angiotensin II-Induced Renal Injury

Introduction: Hypertension (HT) and kidney disease is increasingly recognized as a global public health problem. Angiotensin II (AngII) induces endothelin-1 (ET-1), and ET-1 is a key mediator of kidney fibrosis. Hypothesis: Inhibition of ET-1 may contribute to modulation of HT and renal injury induced by angiotensin II. Methods: In addition to wild-type (WT) mice, we also used IL-1 receptor antagonist-deficient (IL-1Ra -/- ) mice that were prone to AngII-induced renal inflammation, because WT (C57BL) mice were genetically resistant to renal injury in response to AngII. Both mice were infused with AngII (1000ng/kg/min) using subcutaneous osmotic pumps for 14 days. Results: Systolic blood pressure in IL-1Ra -/- mice significantly increased compared with WT mice (197±5 vs 169±9 mmHg, p&lt;0.05). Furthermore, renal preproendothelin-1 mRNA expression and serum levels of ET-1 were also significantly higher in IL-1Ra -/- mice (p&lt;0.05). Immunostaining revealed that ET-1 was elevated in glomeruli and tubules in the cortex of IL-1Ra -/- mice compared with WT mice (Figure upper panels: ET-1 staining), indicating elevated ET-1 might contribute to glomerular injury (Figure middle panels: PAS staining) and intratubule fibrosis (Figure lower panels: Elastica Masson staining) detected in the histological analysis. Finally, we investigated whether pharmacological inhibition of ET receptors could prevent AngII-induced renal injury in IL-1Ra -/- mice. Bosentan significantly decreased AngII-induced HT, and protected renal injury in IL-1Ra -/- mice. On the other hand, treatment of hydralazine, an antihypertensive agent, did not suppress renal damage in AngII-infused IL-1Ra -/- mice in spite of improvement of HT. Conclusions: Our results indicate that inhibition of ET-1 might protect AngII-induced renal inflammation beyond an antihypertensive therapy, suggesting that we might be required to develop new strategies for blocking ET-1 to prevent hypertensive renal injury.

The Association of Endothelin-1 with Early and Long-Term Mortality in COVID-19.

(1) Background: Endothelial dysfunction is a key mechanism in the pathogenesis of COVID-19. High endothelin-1 during COVID-19 is associated with severe complications and increased mortality rates during hospitalization. This study is aimed to investigate the association of endothelin-1 levels with the risk of 30-day and 12-month all-cause mortality in patients with prior COVID-19. (2) Methods: A prospective study was conducted involving patients with COVID-19 in Karaganda, Kazakhstan. The level of endothelin-1 in the blood serum was evaluated by ELISA. Univariate and multivariate Cox regression was used to determine factors and significance of endothelin-1 associated with the risk of mortality within 30 and 365 days from hospitalization. (3) Results: The median endothelin-1 was higher in the group of patients who passed away within 30 days. The group showed statistically significant differences when compared to healthy volunteers from the control group (p = 0.0001), surviving patients (p = 0.001), and those who passed away within a year (p = 0.002). (4) Conclusions: Endothelin-1 levels are associated with increased mortality risk during the acute period of COVID-19, while plasma endothelin-1 level association with COVID-19 survivor mortality risk does not persist after 12 months.

Serum endothelin-1 level among adult Indonesian females with obesity: a nested cross-sectional study from Universitas Gadjah Mada Health and Demographic Surveillance System, Sleman, Indonesia

Serum endothelin-1 level among adult Indonesian females with obesity: a nested cross-sectional study from Universitas Gadjah Mada Health and Demographic Surveillance System, Sleman, Indonesia