Serum Urotensin II Levels Are Elevated in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has become major public concern and is continuously investigated in new aspects of pathophysiology and management. Urotensin II (UII) is a powerful vasoconstrictor with a role in cardiovascular diseases. The main goal of this study was to evaluate serum UII levels in OSA patients and matched controls. A total of 89 OSA patients and 89 controls were consecutively enrolled. A medical history review and physical examination of the participants was conducted, with polysomnography performed in the investigated group. UII levels and other biochemical parameters were assessed according to the standard laboratory protocols. The median AHI in the OSA group was 39.0 (31.4-55.2) events/h, and they had higher levels of hsCRP when compared to control group (2.87 ± 0.71 vs. 1.52 ± 0.68 mg/L; p < 0.001). Additionally, serum UII levels were significantly higher in the OSA group (3.41 ± 1.72 vs. 2.18 ± 1.36 ng/mL; p < 0.001), while positive correlation was found between UII levels and hsCRP (r = 0.450; p < 0.001) and systolic blood pressure (SPB) (r = 0.317; p < 0.001). Finally, multiple regression analysis showed significant association of UII levels with AHI (0.017 ± 0.006, p = 0.013), SBP (0.052 ± 0.008, p < 0.001) and hsCRP (0.538 ± 0.164, p = 0.001). As UII levels were associated with blood pressure and markers of inflammation and OSA severity, it might play an important role in the complex pathophysiology of OSA and its cardiometabolic complications.

The Association of Passive Smoking and Serum Urotensin-II Levels in Children.

Urotensin-II (UT-II) is the most powerful vasoconstrictor agent and is known to play a role in heart failure, diabetes, pulmonary hypertension and asthma. The effect of passive smoking on UT-II levels is unknown. The present study aims to evaluate serum UT-II levels in children exposed to passive smoke. The study included a total of 120 children; 47 children not exposed to passive smoke were included in Group 1 (control group), and 73 children exposed to passive smoke were included in Group 2. Serum samples of the participants were stored at -80 °C after centrifugation and were assessed at least two times with high-precision human ELISA kits. Serum UT-II levels were significantly higher in the children exposed to passive smoke than in the children not exposed. Furthermore, Group 2 was grouped according to the number of cigarettes smoked at home per day, type of passive smoking (second-hand smoke or third-hand smoke), and how many people in their family and/or living together smoked. There was a positive correlation between the number of cigarettes they were exposed to per day and serum UT-II levels. Passive smoking in childhood may be associated with high serum UT-II levels.

Dynamic Changes in Plasma Urotensin II and Its Correlation With Plaque Stability.

ABSTRACT: Urotensin II (UII) is involved in the formation of atherosclerosis, but its role in the stability of atherosclerotic plaques is unknown. The purpose of this study was to observe the dynamic changes in plasma UII and analyze its relationship to the stability of atherosclerotic plaques. One hundred thirty-five consecutive patients with acute coronary syndrome (ACS) were enrolled. The plasma UII levels were measured immediately after admission and during three-month follow-up. A vulnerable plaque model was established using local transfection of a recombinant P53 adenovirus into plaques in rabbits fed with a high-cholesterol diet and subjected to balloon arterial injury. The levels of plasma UII were measured weekly. The changes in plasma UII during the formation of atherosclerotic plaques and before and after plaque transfection were observed. The morphology of the plaques and the expression, distribution, and quantitative expression of UII in the plaques also were observed. Our results showed that the levels of plasma UII in patients with ACS at admission were lower than levels observed at the three-month follow-up. UII dynamic changes and its correlation with plaque stabilities were further verified in rabbits with atherosclerotic vulnerable plaques. The UII levels in rabbits were significantly decreased immediately after the P53 gene transfection, which led to plaque instability and rupture. These results suggested that UII expression was down-regulated in ACS, which may be related to its ability to modulate mechanisms involved in plaque stability and instability.

Urotensin-II, oxidative stress, and inflammation increase in hypertensive and resistant hypertensive patients.

Objective: Hypertension is a multi-factorial process prevalent in developed as well as in developing countries. Urotensin-II, different antioxidants, free radicals, and inflammatory biomarkers play an essential role in the cardiovascular system. The aim of this study is to investigate Urotensin-II, oxidative stress, and inflammation markers in normotensive, hypertensive, and resistant hypertensive patients. Methods: Fifty resistance hypertensive (rHT) patients, 50 hypertensive patients, and 50 age gender matched normotensive controls (NT-control) were enrolled. Urotensin-II (UII), total oxidant status (TOS), total antioxidant status (TAS), native thiol (NT), total thiol (TT), disulfide (DIS), interleukin 1 beta (IL1ß), interleukin 6 (IL6), tumor necrosis factor-alpha (TNFα), high sensitive c reactive protein (hsCRP), high-density lipoprotein (HDL) low-density lipoprotein (LDL), and total cholesterol (TC) were evaluated. Results: Serum levels of UII, IL1ß, IL6, TNFα, DIS, TOS, and OSI were found higher in rHT and HT as compared to NT-control (p < .001). On the contrary, serum levels of TT, TAS, and NT were lower in rHT and HT as compared to NT-control (p < .001). While TC, hsCRP, TOS, OSI, UII, IL1ß, IL6, and TNFα levels increase from HT to rHT group (p < .001); TAS and NT levels decrease from HT to rHT group (p < .001). Conclusions: UII levels, oxidative stress, and inflammation are higher in rHT and HT, while antioxidants and thiol levels are lower than the NT-control. Our study clearly showed that rHT and HT are more susceptible to impaired states of antioxidants, oxidative stress, and free radicals.

Urotensin II and urantide exert opposite effects on the cellular components of atherosclerotic plaque in hypercholesterolemic rabbits.

Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg-1· h-1) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque.

Urotensin 2 and Oxidative Stress Levels in Maternal Serum in Pregnancies Complicated by Intrauterine Growth Restriction.

Background and objectives: In this study, the aim was to investigate Urotensin 2 (U-II) levels and oxidant/antioxidant system parameters in pregnancies with intrauterine growth restriction (IUGR). Materials and Methods: A total of 36 healthy, pregnant women who had not been diagnosed with IUGR and 36 pregnant women who had been diagnosed with IUGR at the Obstetrics and Gynecology Outpatient Clinic at Gaziantep University Hospital were enrolled in this study. The serum total antioxidant status (TAS), total oxidant status (TOS), thiol-disulfide levels, U-II measurements, and oxidative stress index (OSI) calculations were carried out at the biochemistry laboratory at Gaziantep University. Results: According to this study, there was no statistically significant difference between the group with IUGR and the control group of healthy, pregnant women in terms of total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), native thiol, total thiol, disulfide, disulfide/native thiol, disulfide/total thiol, native thiol/total thiol, and U-II values. There was, however, a positive linear correlation between TOS and total thiol levels in the group with IUGR (p = 0.021, r = 0.384), and a positive linear correlation between OSI and total thiol values in the control group (p = 0.049, r = 0.330). In addition, there was a negative correlation between disulfide levels and gestational weeks at birth in the group with IUGR (p = 0.027, r = 0.369). Conclusions: Consequently, there was no significant difference between the control group and the group with pregnancies complicated by idiopathic IUGR in terms of serum oxidant/antioxidant system parameters and U-II levels. It is necessary to conduct more extensive studies evaluating placental, maternal, and fetal oxidative stress in conjunction in order to investigate the role of oxidative stress in IUGR.

Is elevated urotensin II level a predictor for increased cardiovascular risk in subjects with acromegaly?

PURPOSE: Acromegaly is a rare disorder existed in the result of overproduction of growth hormone (GH). The disorder is associated with increased cardiovascular risk factors and metabolic abnormalities. Urotensin II (UII), a secreted vasoactive peptide hormone, belonging somatostatin superfamily, plays an essential role in atherosclerosis and glucose metabolism. The aim of this study was to ascertain whether circulating UII levels are altered in subjects with acromegaly, and to describe the relationship between UII and hormonal or cardiometabolic parameters. METHODS: This cross-sectional study included 41 subjects with active acromegaly, 28 subjects with controlled acromegaly, and 37 age- and BMI-matched controls without acromegaly. Hormonal and metabolic features of the subjects as well as carotid intima media thickness (cIMT) and epicardial fat thickness (EFT) were defined. Circulation of UII levels was determined via ELISA. RESULTS: Both active and controlled acromegalic subjects showed a significant elevation of circulating levels of UII with respect to controls. There was no remarkable difference in circulating levels of UII between active and controlled acromegalic groups. Both cIMT and EFT were remarkably increased in acromegaly subjects comparing to controls. UII positively correlated with cIMT, EFT, BMI, and HOMA-IR. There was no correlation between UII and GH, insulin-like growth factor-1. According to the results obtained from regression models, UII levels independently predicted cIMT and EFT. CONCLUSION: Elevated UII levels are associated with severity of cardiovascular risk factors including cIMT and EFT in acromegalic subjects.

The relationship between urotensin II and insulin resistance in women with gestational diabetes mellitus.

AIM: Urotensin II (UII), a pluripotent vasoactive peptide, plays a crucial role in development of insulin resistance. Gestational diabetes mellitus (GDM) is a metabolic disorder associated with insulin resistance. The aims of the current study were to compare UII levels in women with or without GDM and to investigate the relationship between UII and insulin resistance in women with GDM. METHODS: A total of 84 women were recruited in this case-control study (42 women with GDM and 42 age- and body mass index (BMI)-matched pregnant women without GDM as controls). GDM was diagnosed by a 2-h 75-g oral glucose tolerance test over a period of 24-28 gestational weeks. Circulating UII levels were assessed via the ELISA method. The metabolic parameters of the recruited women were also determined. RESULTS: The circulating levels of UII in women with GDM were higher than in controls (11.56 ± 4.13 vs. 7.62 ± 3.45 ng/ml, P < 0.001). UII showed a positive correlation with insulin resistance marker (HOMA-IR), fasting blood glucose, and BMI. Moreover, according to the results of multiple linear regression analyses, UII was independently related to HOMA-IR. Additionally, the binary logistic analysis revealed that the women with the highest tertile of UII levels showed increased risk for GDM by comparison with those women with the lowest tertile of UII levels. CONCLUSION: Elevated UII levels are associated with insulin resistance in women with GDM.

Clinical significance of increased urotensin II levels in acute myocardial infarction.

We aimed to study urotensin II (UII) in acute myocardial infarction (AMI) patients before and after percutaneous coronary intervention (PCI) and to investigate its interaction with angiotensin II (ATII) in post-AMI myocardial remodeling. In this clinical study, 63 AMI patients and 66 controls were included. Levels of UII, ATII, and NT-B-type natriuretic peptide (NT-BNP) were determined. Participants were followed up for 2 years to observe clinical outcomes. In cell biology experiments, ATII and UII were added into cardiomyocytes and fibroblasts individually or in combination. Effects of ATII and UII on cardiac hypertrophy and fibrosis were observed. UII levels increased significantly after AMI (P < 0.001), especially after PCI (P = 0.0009), and was an independent predictor of death (OR 0.007, P = 0.005). UII correlated negatively with hypertension risk stratifications (P = 0.047) and the number of coronary artery lesions (P = 0.029), whereas it correlated positively with left ventricular ejection fraction (P = 0.0395). Myocardial ERK phosphorylations (P = 0.0041) were promoted and the expressions of cardiac hypertrophy-related genes (BNP, ANP) were upregulated in cells treated with ATII and UII (P < 0.005). The ATII+UII group also had significant increases of matrix metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP9), and fibronectin expressions, as well as collagen type I, III, MMP2, and MMP9 gene transcriptions (all P < 0.05). The UII level rose in AMI and was a predictor of death, but at the right concentration it may also have a cardioprotective role. Our findings suggest that UII and ATII have synergistic effects on cardiomyocyte remodeling. UII may play a role in the myocardial healing process post-AMI.

[Effects on cervical spondylosis of vertebral artery type and the concentrations of plasma NPY and UII in the patients treated with the modified acupuncture at unilateral/bilateral Renying (ST 9)].

OBJECTIVE: To observe the differences in the clinical therapeutic effects on cervical spondylosis of vertebral artery type (CSA) between the modified acupuncture and the routine acupuncture at unilateral/bilateral Renying (ST 9) as well as the impacts on the concentrations of plasma neuropeptide Y (NPY) and urotensinⅡ(UⅡ) in the patients. METHODS: A total of 160 patients were divided into a modified bilateral acupuncture group, a modified unilateral acupuncture group, a routine bilateral acupuncture group and a routine unilateral acupuncture group, 40 cases in each one according to the random number table. In the modified bilateral acupuncture group, the modified acupuncture was applied bilaterally to Renying (ST 9). In the modified unilateral acupuncture group, the modified acupuncture was applied unilaterally to Renying (ST 9). In the routine bilateral acupuncture group, the routine acupuncture was applied bilaterally to Renying (ST 9). In the routine unilateral acupuncture group, the routine acupuncture was applied unilaterally to Renying (ST 9). The treatment was given once every day, continuously for 6 days as one course. Two courses of treatment were required at the interval of 1 day. In each group, before and after treatment, we observed the peak systolic blood flow velocity (Vs) of the vertebral artery (VA) and the basilar artery (BA), cervical vertigo symptoms and functional assessment scales (ESCV) and the concentration of plasma NPY and UⅡ. The clinical therapeutic effects were compared among the groups. RESULTS: After treatment, the clinical therapeutic effect in the modified bilateral acupuncture group was 90.0% (36/40), which was better than 80.0% (32/40) in the modified unilateral acupuncture group, 77.5% (35/40) in the routine bilateral acupuncture group and 65.0% (26/40) in the routine unilateral acupuncture group (all P<0.05). After treatment, Vs of VA and BA was improved remarkably in every group (all P<0.01), and the result in the modified bilateral acupuncture group was higher than those in the other groups (all P<0.01). After treatment, ESCV scores were all increased remarkably in every group (all P<0.01). ESCV score and improvement index in the modified bilateral acupuncture group were all higher than those in the other groups (P<0.05, P<0.01). After treatment, the concentrations of plasma NPY and UⅡ were all reduced remarkably in every group (all P<0.01) and the differences were significant among the groups (all P<0.01). CONCLUSION: The modified bilateral acupuncture at Renying (ST 9) effectively regulates the blood supply of the vertebral basilar artery and improves the cerebral circulation. The effects are superior to those of the unilateral acupuncture at Renying (ST 9).

The role of human urotensin-II in patients with hypertrophic cardiomyopathy.

OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a genetic condition with the hallmark feature of left ventricular hypertrophy. Human Urotensin-II (hUT-II) is regarded as a cardiovascular autacoid/hormone, and it has cardiac inotropic and hypertrophic properties. Aims of this study were to elucidate the clinical significance of serum hUT-II levels as a potential new biomarker in patients with HCM. METHODS: This study included 40 HCM patients (60% males and 40% females) and were compared to 30 healthy control subjects (47% males and 53% females. All patients underwent extensive clinical, laboratory, and echocardiographic. Blood samples were taken to test for serum hUT-II levels by commercial ELISA Kit. RESULTS: Serum hUT-II was significantly higher (p < 0.01) in patients with HCM (15.8 ± 2.1 pmol/L) compared with healthy controls (3.3 ± 1.7 pmol/L). With regard to HCM patient, Serum hUT-II levels were significantly higher in the female with 16.3 ± 1.9 pmol/L than the male with 15.4 ± 2.2 pmol/L (p < 0.05). Among echocardiographic parameters, hUT-II was negatively associated with ejection fraction (r = -0.160, p = 0.324). CONCLUSION: Results of the first study indicated that serum hUT-II levels were markedly elevated in patients with HCM. Serum hUT-II is a novel biomarker parameter that has clinical use in patients with the severity of LVH.

Urotensinergic system genes in experimental subarachnoid hemorrhage / El sistema urotensinérgico en un modelo experimental de hemorragia subaracnoidea

Objective: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. Design: An experimental study was carried out. Setting: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). Participants: 96 Wistar rats: 74 SAH and 22 sham intervention animals. Interventions: Day 1: blood sampling, followed by the percutaneous injection of 100μl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. Main variables of interest: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. Results: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) today 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). Conclusion: The urotensinergic system is upregulated on day 5 in an experimental model of SAH (AU)

Objetivo: El vasoespasmo cerebral, una de las principales complicaciones secundarias a hemorragia subaracnoidea (HSA), se caracteriza por una constricción arterial que tiene lugar principalmente entre el día 4 y la segunda semana. La urotensina-II (U-II) ha sido definida como el péptido con mayor capacidad vasoconstrictora en mamíferos. Quisimos analizar los niveles séricos de U-II, así como los niveles de expresión de los genes de U-II, péptido relacionado con urotensina y receptor de urotensina, en un modelo murino experimental de HSA. Diseño: Estudio experimental. Ámbito: Quirófano experimental del Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío. Participantes: Noventa y seis ratas Wistar: 74 con inyección percutánea de sangre (HSA), 22 con inyección percutánea de 100μL de salino (Sham). Intervenciones: Día 1: extracción de muestras de sangre. Posteriormente, inyección percutánea de 100μL de salino (Sham) o de sangre (HSA) en el espacio subaracnoideo. Día 5: extracción de muestras de sangre y sacrificio del animal. Principales variables de interés: Peso, mortalidad precoz, niveles séricos de U-II, valores de ARNm de U-II, péptido relacionado con urotensina y receptor de urotensina. Resultados: Observamos un incremento en los niveles de U-II sérica en el grupo HSA desde el día 1 (0,62pg/mL [RI 0,36-1,08]) al día 5 (0,74pg/mL [RI 0,39-1,43]) (p<0,05); pero no observamos tal diferencia en el grupo Sham (0,56pg/mL [RI 0,06-0,83] día 1; 0,37pg/mL [RI 0,23-0,62] día 5) (p=0,959). Se encontraron diferencias en los niveles de U-II entre ambos grupos al quinto día (p<0,05). El análisis de curvas ROC demostró que la U-II sérica al quinto día (AUC=0,691), ARNm de péptido relacionado con urotensina (AUC=0,706) y ARNm de receptor de urotensina (AUC=0,713) podían discriminar entre ratas Sham y HSA. Además, definimos un rango de normalidad para los niveles de U-II séricos en ratas: 0,56pg/mL (RI 0,06-0,83). Conclusión: Este estudio demuestra por primera vez que el sistema urotensinérgico ve incrementada su expresión en el quinto día en un modelo de HSA (AU)

Expressions of irisin and urotensin II and their relationships with blood pressure in patients with preeclampsia.

The aims of this study are to observe irisin and urotensin II (UII) levels in serum and placenta in normal pregnant and preeclamptic women and investigate the relationship between expressions irisin and UII, and their association with blood pressure. A total of 67 pregnant subjects were recruited, including 31 healthy and 36 preeclamptic pregnant women. Serum irisin and UII concentrations were measured. Expressions of fibronectin type III domain-containing protein 5 (FNDC5) (irisin precursor) and UII in placenta specimens were performed. There was no significant difference of serum irisin levels between severe preeclamptic (SPE)) patients, mild preeclamptic (MPE) patients and normal controls, while serum UII was significantly higher in preeclamptic women than normal pregnancy. There was no relationship between serum UII and irisin levels. In patients with preeclampsia, serum irisin was negatively associated with systolic and diastolic blood pressure(r = -0.350, P = 0.004, r = -0.307, P = 0.011), while serum UII was positively associated with systolic blood pressure (r = 0.291, P = 0.031). Serum irisin, UII, urinary protein level, BMI and serum creatinine were the independent determinants of blood pressure in preeclampsia by multiple regression analysis. Protein expression of FNDC5 and UII was upregulated in placenta of patients with SPE and positively correlated with systolic blood pressure and urinary protein level. We firstly verify that serum irisin and placental irisin precursor expressions have differently correlated with blood pressure. Expressions of irisin and urotensin II have relationships with blood pressure in patients with preeclampsia.

Plasma Urotensin II levels in children and adolescents with chronic kidney disease: a single-centre study.

BACKGROUND: Increased plasma Urotensin II (UII) levels have been found in adults with renal diseases. Studies in children are scarce. The objective of the study is to estimate plasma UII levels in subjects with chronic kidney disease (CKD) stages 3 to 5 and renal transplant recipients (RTR). In addition, the correlation of UII with anthropometric features and biochemical parameters was assessed. METHODS: Fifty-four subjects, aged 3 to 20 years old, 23 with CKD, 13 with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) and 18 RTR were enrolled. A detailed clinical evaluation was performed. Biochemical parameters of renal and liver function were measured. Plasma UII levels were measured in all patients and in 117 healthy controls, using a high sensitive enzyme immunoassay (EIA) kit. All data were analyzed using STATA™ (Version 10.1). RESULTS: Median UII and mean log-transformed UII levels were significantly higher in CKD and RTR patients compared to healthy subjects (p < 0.001). HD patients had higher but not statistically significant UII and log-UII levels than controls. UII levels increased significantly at the end of the HD session and were higher than controls and in line to those of other patients. The geometric scores of UII in HD (before dialysis), CKD and RTR patients increased respectively by 42, 136 and 164% in comparison with controls. Metabolic acidosis was associated with statistical significant change in log-UII levels (p = 0.001). Patients with metabolic acidosis had an increase in UII concentration by 76% compared to those without acidosis. CONCLUSIONS: Children and adolescents with CKD, particularly those who are not on HD and RTR, have significantly higher levels of UII than healthy subjects. UII levels increase significantly at the end of the HD session. The presence of metabolic acidosis affects significantly plasma UII levels.

[Changes in serum chromogranin A and urotensin II levels in children with chronic heart failure].

OBJECTIVE: To examine the changes in serum chromogranin A (CgA) and urotensin II (U II) levels in children with chronic heart failure (CHF) and their clinical significance. METHODS: A total of 58 children with CHF, among whom 17 had endocardial fibroelastosis (EFE) and 41 had dilated cardiomyopathy (DCM), were selected as CHF group, and 20 healthy children were selected as control group. Serum levels of CgA and U II were measured using enzyme-linked immunosorbent assay, and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined by bi-directional lateral flow immunoassay. Ventricular remodeling indices were measured using echocardiography. The correlation between serum CgA and U II levels and ventricular remodeling was evaluated by Pearson correlation or Spearman's rank correlation analysis. RESULTS: There were no significant differences in serum CgA and NT-proBNP levels between children with grade II heart function and the control group (P>0.05). However, the serum CgA and NT-proBNP levels gradually increased as the heart function grade increased, and were significantly higher in grade III and IV children compared to those in the control group (P<0.05). U II levels were lower in children with grade II, III, or IV heart function than those in the control group (P<0.05), and significantly decreased with the aggravation of CHF (P<0.05). There were no significant differences in CgA and U II levels between patients with EFE and DCM (P>0.05). Serum CgA concentration was positively correlated with left ventricular mass index (LVMI), NT-proBNP, and cardiac function classification (r=0.279, 0.649, and 0.778 respectively; P<0.05), but was negatively correlated with left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and U II (r=-0.369, -0.322, and -0.718 respectively; P<0.05). Serum U II concentration was negatively correlated with NT-proBNP and cardiac function classification (r=-0.472 and -0.591 respectively; P<0.05), but was not correlated with LVMI, LVEF, and LVFS (P>0.05). CONCLUSIONS: CgA may play a role in ventricular remodeling in children with CHF. Serum CgA and U II may serve as a reference for the diagnosis and functional classification of heart failure.

Urotensinergic system genes in experimental subarachnoid hemorrhage.

OBJECTIVE: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. DESIGN: An experimental study was carried out. SETTING: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). PARTICIPANTS: 96 Wistar rats: 74 SAH and 22 sham intervention animals. INTERVENTIONS: Day 1: blood sampling, followed by the percutaneous injection of 100µl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. MAIN VARIABLES OF INTEREST: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. RESULTS: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). CONCLUSION: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

Comparison of two competitive enzyme immunoassay kits for quantification of plasma Urotensin-II in rats.

Changes in Urotensin-II (U-II) concentration, a potent vasoconstrictor peptide, have been detected in various pathologies, but it has been impossible to define a normality range. We aimed to analyze the concordance and interchangeability between two enzyme immunoassay methods developed by Phoenix Pharmaceuticals, Inc. to measure U-II plasma concentration in rats: ELISA and fluorescent EIA. Assays resulted positively correlated (r = 0.850; p < 0.01). There was a significant difference between assays values (p < 0.001). The analysis of agreement (Bland and Altman plot) stated that the mean of the differences was 2.055 (SD ± 0.588). Hence, we concluded that the two U-II assays were correlated but not interchangeable.

Plasma urotensin II levels in primary Raynaud's phenomenon and systemic sclerosis

Background/aim: The pathogenesis of Raynaud's phenomenon (RP) has not yet been fully elucidated. RP is characterized by exaggerated cold-induced vasoconstriction. Urotensin II (UII) is a potent vasoconstrictor. The aim of the present study was to evaluate plasma UII levels in both primary RP and secondary RP associated with systemic sclerosis (SSc).Materials and methods: Fifteen patients with primary RP, 30 patients with RP secondary to SSc, and 30 healthy controls (HC) were included in the study. Raynaud condition scores (RCS) were determined in the primary RP and SSc groups. Modified Rodnan skin score (MRSS) was determined for the SSc patients. Plasma UII level was analyzed by the ELISA method. Results: When compared to the HC group, plasma UII level was lower in the secondary RP group, but not in the primary RP group. Plasma UII level was not directly related to RCS in either the primary or secondary RP group. Moreover, it was not correlated with MRSS in the secondary RP group.Conclusion: The results of the present study suggest that UII is not associated with primary RP. Its level was lower in the secondary RP (SSc) patients. Therefore, it can be concluded that decreased UII level is related to SSc instead of RP.

Plasma urotensin-2 level and Thr21Met but not Ser89Asn polymorphisms of the urotensin-2 gene are associated with migraines.

BACKGROUND: Urotensin-II (U-II) is a peptide recognized by its potent vasoconstrictor activity in many vascular events, however the role of urotensin-II in migraine has not been considered yet. The molecular mechanisms and genetics of migraine have not been fully clarified yet, but it is well-known that vascular changes considerably contribute in pathophysiology of migraine and also its complications. The aim of this study was to analyze the plasma U-II levels along with genotype distributions and allele frequencies for UTS2 Thr21Met and Ser89Asn polymorphisms among the patients with migraine without aura (MWoA). METHODS: One hundred eighty-six patients with MWoA and 171 healthy individuals were included in this study. Plasma U-II levels were measured in attack free period. The genotype and allele frequencies for the Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms in the UTS2 gene were analyzed. RESULTS: Plasma U-II levels were significantly higher in MWoA patients (p = 0.002). We detected a significant association between the T21M polymorphism in the UTS2 gene and migraine (53.8 % in patients, 40.4 % in controls, p = 0.035), but not with S89N polymorphism (p = 0.620). A significant relationship was found between U-II levels and MIDAS score (ß = 0.508, p = 0.001). CONCLUSION: Our study suggests that U-II may play a role in migraine pathogenesis; also Thr21Met polymorphism was associated with the risk of migraine disease. Further studies are needed for considering the role of U-II in migraine pathophysiology and for deciding if UTS2 gene may be a novel candidate gene in migraine cases.