Evaluation of Endothelial Dysfunction in Bipolar Affective Disorders: Serum Endocan and Urotensin-II Levels

OBJECTIVE: This study investigated changes in urotensin-II (U-II) and endocan levels which can be used as an early biological marker of endothelial injury in the episode and remission phases of bipolar affective disorder (BAD). METHODS: We compared endocan and U-II levels, which has been shown to be closely associated with neurotransmitter systems in addition to continuity of endothelial structure and inflammatory response, in patients with BAD in remission for at least one year (n=42) and in patients still in manic or depressive episodes (n=16) with healthy controls (n=30). RESULTS: Both endocan and U-II levels were significantly higher in the bipolar patients than in the controls. Endocan and U-II levels were also significantly correlated with one another (p=0.000, r=0.833). Both endocan (p=0.000) and U-II levels (p=0.000) were significantly higher in the bipolar attack group compared to the subjects in remission, and in the remission group compared to the controls. CONCLUSION: In this study we determined significantly higher endocan and U-II levels in BAD compared to the controls, while serum endocan and U-II levels of patients undergoing attacks were also significantly higher than those of the controls and also those of patients in remission.

Mechanisms underlying the urotensin Ⅱ-induced proliferation of and α-smooth muscle actin expression in human dermal fibroblasts / 中华皮肤科杂志

Objective To evaluate the effects of urotensin Ⅱ on cell proliferation of and α-smooth muscle actin (α-SMA) expression in normal human dermal fibroblasts (NFs),and to explore their regulatory mechanisms.Methods NFs were isolated from foreskin tissues and subjected to primary culture in vitro.Reverse transcription PCR and Western blot analysis were performed to measure the mRNA and protein expression of urotensin Ⅱ and its receptor,respectively.Cell counting kit-8 (CCK-8) assay was conducted to estimate the proliferation of NFs,which were treated with urotensin Ⅱ at different concentrations of 0,10-10,10-9,10-8,10-7 and 10-6 mol/L for 0,6,12,24 and 48 hours separately,and then the optimal concentration and duration of urotensin Ⅱ exposure were selected to be 10-8 mol/L and 24 hours respectively.Some cultured NFs were divided into 5 groups:control group receiving no treatment,U Ⅱ group treated with 10-8 mol/L urotensin Ⅱ,U Ⅱ + nicardipine group treated with 10-8 mol/L urotensin Ⅱ and the calcium channel blocker nicardipine at the concentration of 10-5 mol/L,U Ⅱ + PD98059 group treated with 10-8 mol/L urotensin Ⅱ and the mitogen activated protein kinase (MAPK)inhibitor PD98059 at the concen-tration of 10-5 mol/L,and U Ⅱ + cyclosporine group treated with 10-8 mol/L urotensin Ⅱ and the calcium-dependent protein kinase (CaM PK) inhibitor cyclosporine at the concentration of 10-5 mol/L.After 24-hour treatment,CCK-8 assay was conducted to evaluate the proliferation of NFs in the above groups,real-time fluorescence-based quantitative PCR and Western blot analysis were performed to determine the mRNA and protein expression of α-SMA respectively.Results Urotensin Ⅱ receptor was expressed in NFs,but urotensin Ⅱ was not.The proliferative activity of NFs significantly differed among the control group,U Ⅱ group,U Ⅱ + nicardipine group,U Ⅱ + PD98059 group and U Ⅱ + cyclosporine group (the mean absorbance value at 405 nm:1.036 ± 0.046,1.405 ± 0.158,1.121 ± 0.109,1.192 ± 0.089 and 1.141 ± 0.056,respectively;F =9.587,P ＜ 0.01),and the U Ⅱ group showed significantly higher proliferative activity of NFs compared with the control group,U Ⅱ + nicardipine group,U Ⅱ + PD98059 group and U Ⅱ + cyclosporine group (q =8.263,6.355,4.774 and 5.912,respectively,all P ＜ 0.05).There were significant differences in the mRNA and protein expression of α-SMA among the 5 groups (F =6.351,7.045,both P ＜ 0.01),and the mRNA and protein expression of α-SMA was significantly higher in the U Ⅱ group than in the other 4 groups (all P ＜ 0.05).Conclusion Urotensin Ⅱ may induce the proliferation of and α-SMA expression in NFs through calcium channels,MAPK and CaM PK pathways.

Serum PDGF-BB, sFlt-1 and U-Ⅱ in patients with preeclampsia / 中华检验医学杂志

Objective To explore the clinical diagnostic value of joint detection of serum platelet-derived growth factor BB (PDGF-BB), soluble vascular endothelial growth factor receptor -1 (sFlt-1) and urotensinⅡ( U-Ⅱ) in preeclampsia disease.Methods The cases of obstetric patients suffering from preeclampsia in the Third People′s Hospital of Liaocheng , Shandong Province between October 2012 and April 2014 were enrolled , including 96 cases of mild preeclampsia and 81 cases of severe preeclampsia.Totally 68 cases of normal pregnant women with similar age and gestational age were selected as control group.A case-control study was applied for the following investigations.The concentrations of serum PDGF-BB, sFlt-1 and U-Ⅱwere measured using ELISA.The diagnostic value of PDGF-BB, sFlt-1 and U-Ⅱalone or in combination for preeclampsia was analyzed and evaluated with receiver operating characteristic curve ( ROC) and Logistic regression analysis.Results Serum concentrations of PDGF-BB, sFlt-1 and U-Ⅱin mild preeclampsia group were (80.45 ±21.87)ng/L,(23.03 ±6.67)μg/L and(4.54 ± 1.02)ng/L, and those in severe preeclampsia group were (124.91 ±47.54)ng/L,(35.65 ±12.45)μg/L and(6.29 ±2.31) ng/L, while those in control group were (60.89 ±19.38) ng/L,(17.19 ±7.867)μg/L and ( 3.81 ±1.01 ) ng/L, respectively.The three parameters in mild preeclampsia group and severe preeclampsia group were significantly higher than those in control group ( P<0.01; F value was 79.43, 79.28 and 50.72 respectively ).In the same situation , these three indicators in severe preeclampsia group were significantly higher than those in mild group (P<0.01).Moreover, the AUC of serum PDGF-BB, sFlt-1 and U-Ⅱalone or in combination were 0.821, 0.786, 0.772 and 0.933, respectively.The differences between joint detection and three individual detections were statistically significant ( P<0.05 ) , as combined detection having a sensitivity of 95.7% and a specificity of 86.6%.Conclusion The combined detection of Serum PDGF-BB, sFlt-1 and U-Ⅱ had an important value in early assessment and treatment of preeclampsia.

The examination and the expression of urotensin Ⅱ and their relationship with pre-eclampsia / 国际检验医学杂志

Objective To explore the effect of urotensin Ⅱ (U Ⅱ) in occurrence and development of pre-eclampsia through the examination of U Ⅱ in pre-eclampsia pregnant woman and newborn cord blood and the expression of U Ⅱ mRNA in placenta. Methods 1) The serum U Ⅱ of peripheral blood and newborn cord blood was determined in 40 pre-eclampsia patients and 20 normal pregnant women (control group) by using ELISA method. 2) The U Ⅱ mRNA expression level in placenta tissue was simultaneously examined with RT-PCR method. Results The concentration o{ serum U Ⅱ in pre-eclampia patients was obviously higher than that in control group (P<0.05).2) The U Ⅱ mRNA ex-pression level in placenta tissue in pre-eclampsia patients was obviously higher than that in control group (P<0.05). Conclusion U Ⅱ plays an important role in development of ischemia, anoxemia and atherosclerosis of placenta tissue.

The expression, synthesis and release of Urotensin Ⅱ in hypoxic pulmonary hypertension and its significance / 中国医师杂志

Objective To study the release of synthetic gene expression induced by vasopressin Ⅱ (U Ⅱ ) in hypoxic pulmonary hypertension. Methods Rat model of HPH was establish. RIA was used to observe the different time points of hypoxia in plasma and the dynamic changes of U Ⅱ , ADM content in bronchoalveolar lavage fluid (BALF). The impact of the release of U Ⅱ , as well as the relation-ship among U Ⅱ , ADM and HPH were explored to reveal the role of U Ⅱ in the pathophysiology of HPH. Results Rat HPH model was successfully established. Hypoxia promoted the expression, synthesis and release of U Ⅱ in lung tissue. U Ⅱ involved in the pathogenesis of HPH. HPH took place in the development of U Ⅱand was positive correlated with ADM. Conclusion The two peptides have opposite physiological effects on blood vessel, which suggest that these two peptides play an important role in maintaining the balance between the pul-monary circulation and lung ventilation as well as the stability of pulmonary artery pressure.

Role of urotensin Ⅱ gene in the genetic susceptibility to gestational diabetes mellitus in northern Chinese women / 中华妇产科杂志

Objective To investigate the relationship between the polymorphism of site rs228648 in urotensin Ⅱ gene and the genetic susceptibility to gestational diabetes mellitus in northern Chinese women. Methods Genotyping was conducted to investigate the polymorphism of site rs228648 (G—A) in urotensin Ⅱgene among 70 unrelated gestational diabetes mellitus(GDM) subjects and 70 normal controls. DNA samples isolated from leucocyte of the control and study groups were analyzed for single-nucleotide polymorphisms of the urotensin Ⅱ gene at positions rs228648 using polymerase chain reaction and restriction analysis. Results (1)The distribution of genotype frequencies of site rs228648 accorded with Hardy-Weinberg′s equation law, being colony representative.(2)The frequency of G allele of site rs228648 was 70.7% in GDM group, significantly higher than that in the control group (57.9%, P0.05). (3) Women in control group were more likely to be homozygous for the allele A of site rs228648 than women with GDM. The frequency of A/A genotype of rs228648 was negatively correlated with GDM group. By the logistic procedure, after adjustment by age and gestational weeks, the odds ratio was 0.312 , and Wald Confidence Limites were 0.108 to 0.900 (P= 0.031). Conclusion Urotensin Ⅱ gene may contribute to the genetic susceptibility to gestational diabetes mellitus in northern Chinese population. G allele of site rs228648 is related to GDM possibly, and that homozygosis A of site rs228648 is likely to be an important protecting factor for GDM.

Rat urotensin-II-induced main pulmonary artery contractions are mediated by MAPK * / 中国病理生理杂志

AIM:To investigate rat Urotensin-II(ra t U-II)-induced vasoconstriction of rat main pulmonary arteries and the role of mitogen-activated protein kinase(MAPK). METHODS: The main pulmon ary artery was dissected from the male Sprague -Dawley rats and artery ring width was 3-4 mm. Concentration-response curves wer e gene rated to rat U-II(0 03 nmol/L-30 nmol/L).Inhibitor of MAPK,PD 98059(0 1 ?mol/ L -10 ?mol/L) were added into the medium after rat U-II(30 nmol/L)induced vasoc onstriction had reached plateau to construct the relaxant concentration-respons e curves and their EC 50 and E max . RESULTS: Rat U-II was a potent vasoconstrictor of isolated rat main pulmonary arteries [EC 50 =7 95?0 4 0, E max =(14 28?6 34)% of the response to 60 mmol/L KCl]; PD 98059 caused c oncentration-dependent relaxations of rat U-II precontracted arteries [EC 50 =5 91?0 45, E max =(81 39?13 65)%]. CONCLUSION: Rat U- II was a potent vasoconstrictor of rat main pulmonary arteries and this response was med iated through MAPK.

The alteration of urotensin-II receptors in rat aorta after balloon angioplasty injury / 中国病理生理杂志

AIM: To observe the alteration of urotensin II (UII) receptors and contractile response to UII in rat aorta after balloon angioplasty injury. METHODS: The plasma membrane isolated from balloon injured aorta was used to study the binding of [ 125 I]-UII to the membrane and the contractile potency of UII on rat aorta was assayed. RESULTS: In contrast to the normal aorta, the contractile potency to UII enhanced in balloon injury artery and the calculated maximal number of specific binding sites (Bmax) was increased about 44% and 36% respectively in rat artery after balloon injury 3 and 21 days ( P

Effect of nitric oxide on urotensin-Ⅱ expression in pulmonary arterioles of rats chronically exposed to hypoxia-hypercapnia / 中国病理生理杂志

AIM: To investigate the roles of nitric oxide/L-arginine(NO/L-Arg) pathway and urotensin-Ⅱ(UⅡ) in the development of pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats.METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups(n=10): normal control group(A),hypoxia-hypercapnia+saline group(B),hypoxia-hypercapnia+L-Arg liposome group(C) and hypoxia-hypercapnia+N-nitro-L-arginine methyl ester(L-NAME) group(D).Contents of UⅡ,UⅡ mRNA and receptor of UⅡ(UT) mRNA in pulmonary arterioles were measured with immunohistochemistry analysis and in situ hybridization,respectively.Change of small pulmonary vascular microstructure was also investigated.RESULTS:(1) The mean pulmonary artery pressure(mPAP) and the weight ratio of right ventricle to left ventricle plus septum [RV/(LV+S)] in B and D groups were all higher than those in A group(respectively,P

Expression of urotensinⅡ receptor GPR14 in aorta of apoE knockout mice / 中国病理生理杂志

] AIM: To investigate the expression of the urotensin Ⅱ (UⅡ) receptor GPR14 in the aorta of apoE knockout mouse. METHODS: The expression of GPR14 in the aorta of apoE knockout C57BL/6J mice at various ages (18 weeks, 28 weeks, and 38 weeks old, respectively) was determined with competitive RT-PCR. A binding assay of [ 125 I]-UⅡ on the aortic tissue was also performed in 28 weeks group. RESULTS: We found significant upregulation of GPR14 mRNA at all three ages. Compared with wild type group at the same age, the GPR14 mRNA level in apoE knockout mice increased 54.2% in 18 week group (P

Effect of urotensin II on cultured pulmonary arterial smooth muscle cells of rabbits / 中国病理生理杂志

AIM: The effect of urotensin II (U-II) on proliferation of cultured pulmonary arterial smooth muscle cells (PASMCs) of rabbits and its mechanism are investigated. METHODS: PASMCs were isolated using explant technique. RPASMCs were incubated in serum-free medium with different concentrations of nicardipine, calcimodulin antagonist W 7, PKC inhibitor H 7 or MAPK inhibitor (PD 98059 ), with or without U-II. RPASMC proliferation was examined by MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and by the increase in [ 3H]-thymidine incorporation into DNA. RESULTS: U-II (10 -9 mol/L-10 -7 mol/L) increased A value of PASMCs by MTT assay and [ 3H]-thymidine incorporation in PASMCs in a dose-dependent manner. U-II induced a maximal effect at a concentration of 10 -7 mol/L. A value and [ 3H]-thymidine incorporation rose 42 9% and 68 5% ( P

Effects of human urotension Ⅱ on in vivo mesenteric microcirculation in rats / 中国病理生理杂志

AIM: To investigate the effects of human urotensin Ⅱ (hUII) on in vivo mesenteric microcirculation in rats. METHODS: For recording of microcirculation images in the mesentery, the intestinal loop was mounted on the stage of an intravital microscope equipped with a TV camera. Video images of microcirculation were stored by a video cassette recorder. Temporal changes in internal diameter and microcirculatory velocity of microvesseles were measured by computer using the ImagePro software. The blood flow in intestinal wall was measured with PIMII laser Doppler perfusion Imager (Lisca Sweden). RESULTS: The internal diameters of arterioles and venules in control group were (21.4?2.3) ?m and (38.1?3.6) ?m,respectively. In UII group, the arterioles and venules contracted immediately after treated with UII and up to the peak at 1 min [(14.1?1.4) ?m and (22.2?5.2) ?m vs control,P0.05). The blood flow in intestinal wall increased 1 min after treated with UII and up to high peak at 5 min(6.4?1.1 perfusion unit vs control 4.2?0.9,P

Effects of adrenomedullin on proliferation of vascular smooth muscle cells induced by urotensin Ⅱ / 中国病理生理杂志

AIM: To observe the effect of adrenomedullin(ADM)on proliferation of vascular smooth muscle cells(VSMC) induced by urotensin Ⅱ(UⅡ). METHODS: DNA synthesis of cultured rat aortic VSMC was measured by -TdR incorporation. The activities of mitogen activated protein kinase(MAPK) were determined by isotope tagged with [?- 32 P]-ATP. RESULTS: UⅡ(10 -8 mol/L) significantly increased -TdR incorporation of VSMC and MAPK activities by 38%( P0.05 ), 32%( P0.05 ), 32%( P

Expression of urotensinⅡreceptor GPR14 in cardiovasculature and brain of rats / 第二军医大学学报

Objective: To observe the expression of the G-protein-coupled-receptor 14 (GPR14), urotensinⅡreceptor, in the cardiovascular system and brain of SD rats. Methods: Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the GPR14 mRNA. Results: In cardiovascular system, GPR14 mRNA was detected in the left ventricle, left atrium, thoratic aorta and carotid aorta. The highest level of expression was found in the left ventricle. In the brain, GPR14 mRNA was detected in cortex, hippocampus, hypothalamus and cerebellum, and higher level of expression was found in the cerebellum. Conclusion: GPR14 mRNA expression is found in the cardiovascular and neural tissues of tested rat, suggesting that urotensinⅡ may play an important role in cardiovasculature and central nervous activity.