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.

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.

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.

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.

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.

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.

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.

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.

[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.

Irisin is Associated with Urotensin II and Protein Energy Wasting in Hemodialysis Patients.

AIMS/INTRODUCTION: Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII) is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD) patients. MATERIALS AND METHODS: One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance. RESULTS: The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin) (the natural logarithm of irisin) were UII lean body mass and patients with protein energy wasting. CONCLUSIONS: Our results are the first to provide the clinical evidence of the association among irisin, UII, and protein energy wasting. Our results hint that UII and protein energy wasting might inhibit the release or synthesis of irisin from skeletal muscles in HD patients.

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.

The role of the UTS2 gene polymorphisms and plasma Urotensin-II levels in breast cancer.

Breast cancer is the most common malignancy predominantly affecting women. To date, numerous numbers of studies were reported novel genetic contributors with diagnostic, prognostic, and therapeutic potential for the breast carcinogenesis. However, the role of urotensin-II in breast carcinogenesis has not been elucidated yet. Urotensin-II is a somatostatin-like cyclic tiny peptide identified by its potent vasoconstrictor activity. Soon after its discovery, its involvement in many disease states as well as its expression in various tissues including the tumors have been demonstrated. Moreover, there is strong evidence that suggest urotensin-II as the significant contributor of angiogenesis as well as cell proliferation and tumor biology. In this study, enzyme-linked immunosorbent assay (ELISA) and restriction fragment length polymorphism analysis were used to evaluate plasma levels of urotensin-II and Thr21Met and Ser89Asn polymorphisms of UTS2 gene in breast cancer patients. In the present case-control study, we noticed a significant decrease in the levels of urotensin-II protein in the plasma of the breast cancer patients (p < 0.05). Also, Thr21Met polymorphism in the UTS2 gene was associated with the risk of developing breast cancer (p < 0.0001), whereas the genotype frequency of Ser89Asn was found to be similar in patients and controls (p > 0.05). In addition, we demonstrated the gradual decreasing of urotensin-II protein levels from TT and TM to MM genotypes. In conclusion, these results strongly suggest that urotensin-II could contribute to breast carcinogenesis and Thr21Met polymorphism can be an important risk factor in developing breast tumors.

Association between essential hypertension and three vasoactive peptides, urotensin II, endothelin and adrenomedullin.

AIM: The aim of the study is to measure the vasoactive peptides, urotensin II (UII), endothelin (ET) and adrenomedullin (ADM) in a well-characterized population of normal controls and patients with essential hypertension, and to study their association with this disease. METHODS: The contents of plasma UII, ET and ADM were measured by radioimmunoassay in 40 normal controls and 120 patients with essential hypertension. Echocardiographic examinations were performed using an ultrasonic system, and the left ventricular end diastolic diameter (LVEDd) along with the left ventricular posterior wall thickness (LVPWT) and interventricular septal thickness (IST) were determined. The left ventricular mass index (LVMI) was calculated according to the method reported by Devereux et al. RESULTS: Plasma UII, ET and ADM contents were increased in patients than healthy controls (3.28 ± 1.257 pmol/L vs. 1.80 ± 0.639 pmol/L, p < 0.01), and correlated with the severity of hypertension in patients. Besides, all the three vasoactive peptides in plasma had significant correlations with SBP, IST, LVPWT, LVMI (p ≤ 0.05), while they showed insignificant associations with LVEDd (p > 0.05). UII was remarkably associated with ADM content, while the association of UII level with LVEDd and ET content were not significant. CONCLUSION: The vasoactive peptides UII, ET and ADM may be involved in the pathophysiologic process of essential hypertension, and function as the indicators for severity of this disease.

Decrease of Urotensin II activity can impact on the volume status in predialysis chronic kidney disease.

Urotensin II (U-II) was thought to be one of the mediators of primary renal sodium retention due to effects on renal sodium excretion. For this purpose, the relationship between U-II and overhydration was investigated. A total of 107 patients were enrolled in the study. According to body compositor monitor analysis, fluid overload up to 1.1 L, was considered normohydration. Patients were divided according to hydration status; overhydrate (n = 42) and normohydrate (n = 65) were studied in both groups. Pulse waveform velocity propagation for arterial stiffness and blood pressure analysis and echocardiographic left ventricular and left atrial indices were performed with known fluid overload-related parameters. U-II levels were measured by using Human ELISA kit. In overhydrated group, U-II levels were significantly lower. All parameters (blood pressure, arterial stiffness parameters, echocardiographic data, age, gender, diabetes, U-II, hemoglobin) correlated with overhydration, were determined by linear regression model (method = enter), when considered together, U-II was found to be an independent predictor from other conventional overhydration-related parameters. Male sex, left ventricular mass index, left atrial volume index, hemoglobin value were found to be independent predictors for overhydration. Considering the association of low U-II levels with adverse cardiovascular events and its role in sodium retention, we think that low U-II levels can be accepted as a potential therapeutic target in patients with hypervolemic cardio-renal syndrome.

Urotensin II inhibited the proliferation of cardiac side population cells in mice during pressure overload by JNK-LRP6 signalling.

Cardiac side population cells (CSPs) are promising cell resource for the regeneration in diseased heart as intrinsic cardiac stem cells. However, the relative low ratio of CSPs in the heart limited the ability of CSPs to repair heart and improve cardiac function effectively under pathophysiological condition. Which factors limiting the proliferation of CSPs in diseased heart are unclear. Here, we show that urotensin II (UII) regulates the proliferation of CSPs by c-Jun N-terminal kinase (JNK) and low density lipoprotein receptor-related protein 6 (LRP6) signalling during pressure overload. Pressure overload greatly upregulated UII level in plasma, UII receptor (UT) antagonist, urantide, promoted CSPs proliferation and improved cardiac dysfunction during chronic pressure overload. In cultured CSPs subjected to mechanical stretch (MS), UII significantly inhibited the proliferation by UT. Nanofluidic proteomic immunoassay showed that it is the JNK activation, but not the extracellular signal-regulated kinase signalling, that involved in the UII-inhibited- proliferation of CSPs during pressure overload. Further analysis in vitro indicated UII-induced-phospho-JNK regulates phosphorylation of LRP6 in cultured CSPs after MS, which is important in the inhibitory effect of UII on the CSPs during pressure overload. In conclusion, UII inhibited the proliferation of CSPs by JNK/LRP6 signalling during pressure overload. Pharmacological inhibition of UII promotes CSPs proliferation in mice, offering a possible therapeutic approach for cardiac failure induced by pressure overload.

New molecule in the etiology of schizophrenia: urotensin II.

AIMS: Urotensin II (U-II) is a cyclic peptide that was first isolated from the caudal neurosecretory system of goby fish. U-II receptors were detected in the vascular endothelium, brain and kidney cortex. Urotensin is by far the most powerful vasoconstrictor identified. U-II molecules were previously isolated from the brain of rats and were shown to have an impact on rat behavior. The aim of the present study was to measure the level of U-II molecule in schizophrenia patients and to investigate whether the U-II level is associated with the etiology of schizophrenia. METHODS: Forty schizophrenia patients who were followed at Gaziantep University Faculty of Medicine Department of Psychiatry Psychotic Disorders Unit and 40 healthy volunteers were enrolled in this study. Blood samples were taken from the antecubital vein after 12-h fasting. U-II level was measured on ELISA. RESULTS: The U-II level in schizophrenia patients was significantly higher than in the control group. U-II level was not different with regard to gender in either group. U-II level was not different between subgroups of schizophrenia. No significant correlation was found between U-II level, Positive and Negative Syndrome Scale and Clinical Global Impression-Severity scale scores. CONCLUSION: U-II level was higher in schizophrenia patients, indicating that U-II level may be related to the etiology of the disease.

Study of urotensin II gene and serum levels in relation to pre-eclampsia.

OBJECTIVE: To verify the relationship between Urotensin II (UII) gene and serum levels and pre-eclampsia (PE). STUDY DESIGN: Prospective case control study. SETTING: Tertiary Obstetric centre and university hospital. SUBJECTS: A total of 80 pregnant women at their third trimester were included, 30 of which were with mild PE, 30 with severe disease and 20 age- and BMI-matched normotensive pregnant women (controls). MATERIALS AND METHODS: UII gene polymorphism as well as UII serum levels were assessed and compared in patients vs. control. RESULTS: No difference was seen between the groups in terms of age or parity at the time of recruitment. A statistically significant difference in the Urotensin II genotype frequencies between patients and control groups was found. The mean serum UII, also showed a significant difference between the studied groups, and control group. Comparing the observed and expected values of UII genotype frequencies in mild, severe PE, and in controls, no significant difference was noted in the homo-mutant, the hetero-mutant or the wild genotypes. CONCLUSIONS: Elevation of UII in the serum of PE patients could be correlated to the severity and/or progression of the disease. The UII genotype frequencies between patients and control groups showed a significant difference, which implies a potential benefit for UII gene or level in serum as a diagnostic or prognostic indicator in pre-eclampsia.