Role of urotensin-ii in saphenous vein graft disease

Abstract Objective: To elucidate the effect of diabetes mellitus (DM) on the atherosclerotic process in saphenous vein grafts by determining urotensin-II (U-II) levels in harvested saphenous veins of patients who underwent coronary artery bypass grafting (CABG). Methods: Coronary artery disease (CAD) patients who underwent CABG were divided into two groups: Group I (eight non-diabetic patients; CAD group) and Group II (13 patients; DM+CAD group). All patients underwent coronary angiography prior to surgery and Gensini score was used to determine the severity of coronary atherosclerosis. Saphenous vein samples were stained with hematoxylin-eosin and U-II, then damage score, H-Score, and vein layer thicknesses were calculated and statistically evaluated. Results: In light microscopic evaluation, significant difference was observed between the groups in terms of endothelial cells damage, internal elastic lamina degradation, and tunica media vascular smooth muscle cells (VSMCs) damage (P<0.001). U-II immunoreactivity was increased in tunica adventitia in the DM+CAD group (P=0.002). The increase in foam cells was directly proportional to the thickening of the subendothelial layer, and this increased U-II immunoreactivity. Gensini score was higher in the DM+CAD group than in the CAD group (P=0.002). Conclusion: Our results show that saphenous vein grafts are already atherosclerotic before they are grafted in CAD patients. This disease is more severe in diabetic CAD patients and these changes can be detected using U-II immunoreactivity.

Effect of urantide on liver function and histomorphology in atherosclerotic rats / 中国病理生理杂志

AIM:To investigate the effect of urantide on the liver function and histomorphology in the rats with atherosclerosis (AS).METHODS:The AS Wistar rat model was induced by intraperitoneal injection of vitamin D3 (VD3) and feeding with high-fat diet.The rats were randomly divided into normal control group, AS model group, positive medicine group and urantide group.The liver function indexes of the rats were measured by biochemical test, and the pathological changes of the aorta and liver of the rats were observed by hematoxylin-eosin (HE) staining.The mRNA expression of urotensinⅡ (UII) and GPR14 at mRNA and protein levels in rat livers was determined by RT-qPCR and Western blot.RESULTS:The levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , γ-glutamyltransferase (γ-GT) , lactate dehydrogenase (LDH) , total bilirubin (TBIL) , indirect bilirubin (IBIL) and alkaline phosphatase (ALP) in AS model group were significantly increased compared with normal control group (P<0.05).The above indexes in urantide group were remarkably decreased compared with AS model group (P<0.05).No change of the levels of direct bilirubin (DBIL) , total protein (TP) , globulin (GLB) and albumin (ALB) in each group was observed.Urantide postponed hepatocyte fatty degeneration and repaired hepatocyte injury in the AS rats.Compared with normal control group, the mRNA and protein levels of UII and GPR14 in the liver were significantly increased in AS model group (P<0.05).With the prolongation of dosing time, the mRNA and protein levels of UII and GPR14 in the liver were significantly decreased in urantide group compared with AS model group (P<0.05).CONCLUSION:Urantide significantly attenuates the liver damage caused by liver fatty degeneration in AS rats.

Effects of total flavones of rhododendra on contractility of rat myocardial cells and its mechanism / 安徽医科大学学报

Objective To investigate the total flavones of rhododendra(TFR) on contractility of rat myocardial cells and its possible mechanism. Methods The contraction amplitude and contraction frequency of primary cultured rat myocardial cells were observed by image analysis system. The intracellular free Ca2 + content was measured by calcium ion imaging system. Results 10 and 100 nmol /L hU Ⅱ significantly accelerated the contraction frequency of myocardial cells,and 10 nmol /L hU Ⅱ increased the contraction amplitude of myocardial cells,but 100 nmol /L hU Ⅱ reduced the contraction amplitude of myocardial cells. TFR 300 mg /L significantly slowed the contraction frequency of rat myocardial cells and increased the contraction amplitude. TFR in the range of 33. 3 ～ 300 mg /L could significantly inhibit the increase of contraction frequency,the decrease of contraction amplitude and the increase of intracellular free Ca2 + content induced by 100 nmol /L hU Ⅱ. Conclusion TFR can slow down the contraction frequency of myocardial cells and increase its contractility,which may be related to the decrease of free Ca2 + content in myocardial cells.

Urotensin II receptor antagonist reduces hepatic resistance and portal pressure through enhanced eNOS-dependent HSC vasodilatation in CCl-induced cirrhotic rats / 医学前沿

Increased serum urotensin II (UII) levels in human cirrhotic populations have been recently shown, but the long-term effects of UII receptor antagonist on the cirrhosis have not been investigated. To investigate the therapeutic effects of urotensin II receptor (UT) antagonist palosuran on rats with carbon tetrachloride (CCl)-induced cirrhosis, the hepatic and systemic hemodynamics, liver fibrosis, the metalloproteinase-13 (MMP-13)/tissue inhibitor of metalloproteinase-1 (TIMP-1) ratio, hepatic Rho-kinase activity, and the endothelial nitric oxide synthase (eNOS) activity are measured in CCl-cirrhotic rats treated with palosuran or vehicle for 4 weeks. Primary hepatic stellate cells (HSCs) are used to investigate the changes in UII/UT expression and the in vitro effect of palosuran. Compared with the vehicle-treated cirrhotic rats, treatment with palosuran can reduce the portal pressure (PP), decrease the risk of liver fibrosis and the level of α smooth muscle actin, collagen-I (COL-I), and transforming growth factor β expression. However, treatment with palosuran can increase MMP-13/TIMP-1, pvasodilator-stimulated phosphoprotein (p-VASP), and p-eNOS expression. Moreover, in vitro UII/UT mRNA expression increases during HSC activation. MMP-13/TIMP-1, COL-I, and p-VASP are inhibited after palosuran treatment. Our data indicate that long-term administration of palosuran can decrease PP in cirrhosis, which results from decreased hepatic fibrosis and enhanced eNOS-dependent HSC vasodilatation.

Effects of urantide on expressions of type IV collagen in thoracic aorta and VSMC of atherosclerotic rats / 吉林大学学报(医学版)

Objective: To investigate the effects of urantide on the expressions of type IV collagen (Col IV) in thoracic aorta and vascular smooth muscle cells (VSMC) in the rats with atherosclerosis (AS), and to clarify its mechanism of prevention and treatment of AS Methods: A total of 180 Wistar rats were randomly divided into normal control group (n=30) and AS model group (n=150). The rat models of AS were established by feeding on high-fat diet or intraperitoneally injecting vitamin Da (VDa). The AS model rats were randomly divided into AS group, fluvestation (Flu) group and urantide group (3, 7, and 14 d groups). The expression of Col IV in thoracic aorta wall of the rats was detected by immunohistochemistry. The levels of hydroxyproline (HYP) in serum and urine of the rats in various groups were measured by ELISA. The VSMC were randomly divided into normal control group, urotensin E (U II 10~smol • L_ 1) group, Flu group and urantide (10~10to 10~" mol • L_ 1) groups. The levels of Col IV in VSMC of the rats in various groups were determined by ELISA. Results: There was a significant difference in the expression levels of Col IV in the irregular plaques of the thoracic aorta of the rats between various groups (F = 3 5 . 0 9, P < 0 . 01). The expression levels of Col IV in thoracic aorta of the rats in AS group were significantly increased compared with normal control group (P < 0 . 01); the intensity and extent of Col IV positive staining in urantide group were lower than those in AS group (P < 0 . 01). There were significant differences in the serum and urine HYP levels between various groups (F = 2 4 . 38, P < 0 . 01; F=26. 72, P < 0 . 01). Compared with normal control group, the serum HYP level of the rats in AS group were significantly increased (P < 0 . 01), and the urine HYP level was significantly decreased (P < 0 . 01). Compared with AS group, the serum HYP levels in urantide groups were significantly decreased (P < 0 . 01) and the urine HYP levels were significantly increased (P < 0. 01), no less than the level in Flu group. The expression levels of Col IV in the culture supernatant of VSMC in the rats in various groups had significantly difference (F = 3 1 . 04, P < 0 . 01). The expression level of Col IV in the culture supernatant of VSMC of the rats in U II group was significantly increased compared with normal control group (P < 0 . 01); the expression levels of Col IV in the culture supernatant of VSMC of the rats in urantide groups were significantly decreased compared with U II group (P < 0 . 05 or P < 0 . 01). Conclusion: Urantide can inhibit the expressions of Col IV in the thoracic aorta and VSMC of the AS rats and alleviate the degree of AS lesions, which provides the experimental evidence for the clinical application of urantide in the treatment of AS.

Effect of urantide on expression of c-jun n-terminal kinase in thoracic aorta tissue of rats with atherosclerosis and its significance / 吉林大学学报(医学版)

Objective: To investigate the effects of Urantide on the expressions of c-Jun N-terminal kinase (JNK) mRNA and protein in the thoracic aorta tissue of the rats with atherosclerosis (AS) • and to elucidate the molecular mechanism and significance of prevention and treatment of AS. Methods: The AS rat models were established by intraperitoneal injection of Vitamin D combined with high-fat diet and control group was set up at the same time. A total of 150 AS model rats were divided into model group, simvastatin group. IJrantide 3 d group. Urantide 7 d group and Urantide 14 d group ( n= 30). The rats in simvastatin group were adminstrated with simvastatin by gavage for 14 d. and the rats in Urantide groups were injected with Urantide by caudal vein for 3. 7. and 14 d. The serum markers of the rats in various groups were detected by automatic biochemical analyzer; the morphology of rat thoracic aorta tissue was observed by HE staining; the expression levels of JNK mRNA and protein in the rat thoracic aorta tissue were detected by immunohistochemical staining. qRT-PCR and Western blotting methods. Results: Compared with control group, the serum levels of triglyceride (TG). total cholesterol (TC) and low density lipoprotein (LDL) of the rats in model group were increased (P<0. 05). and the level of high-density lipoprotein (HDL) was decreased ( P<.0. 05). The HE staining results showed the formation of bubbling cells in the thoracic aorta tissue, rupture of medullary elastic fibers and calcification of the rats in model group; compared with model group, the pathological symptoms of the thoracic aorta tissue of the rats in simvastatin group and Urantide groups were improved. The immunohistochemistry results showed that the JNK positive particles were weakly expressed in the rat thoracic aorta tissue in control group; the expression intensity of JNK in the rat thoracic aorta tissue in model group was increased ( P<0. 05); compared with model group, the expression intensities of JNK in the rat thoracia aorta tissue in Urantide groups were significantly decreased (P∗C0. 05). The qRT-PCR and Western blotting results showed that the expression levels of JNK mRNA and protein in the rat thoracic aorta tissue in model group were significantly increased ( P

Research Progress of Urotensin Ⅱ on Energy Metabolism in Type 2 Diabetes / 中国药学杂志

Urotensin Ⅱ (UⅡ) and urotensin Ⅱ receptor (UTR) have significant effects on the pathogenesis of type 2 diabetes (T2D). UTR, as a G protein-coupled receptor (GPCR), mediates UⅡ signal transduction.The gene polymorphism of UⅡ and UTR is high related to the susceptibility of diabetes, suggesting a relationship between UⅡ system and T2D. UⅡ system can influence the process of T2D by affecting body weight, lipid and glucose metabolism and inflammatory response. UⅡ can also induce insulin resistance by regulating insulin-related signaling pathway or accelerating oxidative stress.Therefore, UⅡ system might be a potential target for T2D treatment.

Urotensin Ⅱ promotes collagen expression in rats cardiac tissues and proliferation of cardiac myofibroblasts in new-born rats / 基础医学与临床

Objective To investigate the effect of urotensin Ⅱ on myocardial fibrosis in rats.Methods The pressure overload animal model was established in rats by abdominal aorta coarctation.The rats were divided into sham operation group,modeled for 4,8 and 12 weeks group.The expression of U Ⅱ,GPR14,col-Ⅰ,col-Ⅲ,and PKA in cardiac tissues was detected by Western blot.Isolated and cultured cardiac myofibroblasts (CFs) from new-born SD rats were treated with U Ⅱ,KT5720 or SB-611812,and then the proliferation of CFs was observed by micro scope and CKK-8.Results The expression of U Ⅱ,GPR14,col-Ⅰ,col-Ⅲand PKA increased markedly in cardiac tissues of model rat,which were time-dependent.U Ⅱ promoted the proliferation of CFs (P＜0.05),which could be inhibited by KT5720 or SB-611812.Conclusions U Ⅱ/UT system promotes the occurring and development of myocardial fibrosis.

A Novel Urotensin II Receptor Antagonist, KR-36996 Inhibits Smooth Muscle Proliferation through ERK/ROS Pathway

Urotensin II (UII) is a mitogenic and hypertrophic agent that can induce the proliferation of vascular cells. UII inhibition has been considered as beneficial strategy for atherosclerosis and restenosis. However, currently there is no therapeutics clinically available for atherosclerosis or restenosis. In this study, we evaluated the effects of a newly synthesized UII receptor (UT) antagonist, KR-36996, on the proliferation of SMCs in vitro and neointima formation in vivo in comparison with GSK-1440115, a known potent UT antagonist. In primary human aortic SMCs (HASMCs), UII (50 nM) induced proliferation was significantly inhibited by KR-36996 at 1, 10, and 100 nM which showed greater potency (IC₅₀: 3.5 nM) than GSK-1440115 (IC₅₀: 82.3 nM). UII-induced proliferation of HASMC cells was inhibited by U0126, an ERK1/2 inhibitor, but not by SP600125 (inhibitor of JNK) or SB202190 (inhibitor of p38 MAPK). UII increased the phosphorylation level of ERK1/2. Such increase was significantly inhibited by KR-36996. UII-induced proliferation was also inhibited by trolox, a scavenger for reactive oxygen species (ROS). UII-induced ROS generation was also decreased by KR-36996 treatment. In a carotid artery ligation mouse model, intimal thickening was dramatically suppressed by oral treatment with KR-36996 (30 mg/kg) which showed better efficacy than GSK-1440115. These results suggest that KR-36996 is a better candidate than GSK-1440115 in preventing vascular proliferation in the pathogenesis of atherosclerosis and restenosis.

Research progress of urotensin II and urotensin II receptor / 药学学报

Urotensin II (UII) is the most potent vasoconstrictor among the identified vasoactive peptides. UII and its receptor (UT), which play varies of physiological roles, are widely expressed in central nerve system and peripheral organs. The change on the expressional level of UII/UT system has been proved to be closely correlated with pathological conditions. Therefore, UII/UT system was considered to be a potential target for treating many diseases. This review article is devoted to the latest research progress of UII/UT system in several aspects including ligand and receptor distribution, physiological activity, characteristics under pathological conditions and antagonist classification.

Blockade of Urotensin II Receptor Prevents Vascular Dysfunction

Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner. In primary human aortic SMCs (hAoSMCs), UII-induced cell proliferation was significantly inhibited by KR-36676 in a concentration-dependent manner. In addition, KR-36676 decreased UII-induced phosphorylation of ERK, and UII-induced cell proliferation was also significantly inhibited by a known ERK inhibitor U0126. In mouse carotid ligation model, intimal thickening of carotid artery was dramatically suppressed by oral treatment with KR-36676 (30 mg/ kg/day) for 4 weeks compared to vehicle-treated group. From these results, it is indicated that KR-36676 suppress UII-induced proliferation of VSMCs at least partially through inhibition of ERK activation, and that it also attenuates UII-induced vasoconstriction and vascular neointima formation. Our study suggest that KR-36676 may be an attractive candidate for the pharmacological management of vascular dysfunction.

Relationship Between Plasma Level of Urotensin II and Stability of Coronary Atherosclerotic Plaque in Patients With Acute Coronary Syndrome / 中国循环杂志

Objective: To observe the relationship between the dynamic changes of plasma levels of urotensin II (UII) and the stability of coronary atherosclerotic plaque in patients with acute coronary syndrome (ACS). Methods: Our research included 2 groups: ACS group,n=135 consecutive patients treated in our hospital from 2013-03 to 2013-08 that including unstable angina pectoris (UAP) sub-group,n=7, non-ST segment elevation myocardial infarction (NSTEMI) sub-group,n=22 and STEMI sub-group,n=106. In addition, there was a Control group,n=48 healthy subjects. Plasma levels of UII, hs-CRP and NT-proBNP were examined and compared among different groups at different time points. Results: Compared with Control group at immediate admission, ACS group had increased plasma level of UII (39.82 ± 22.28) pg/ml vs (26.88 ± 6.09) pg/ml,P Conclusion: Plasma levels of UII have been changing in different type of ACS patients at immediate admission, UII presented decreasing trend from UAP to NSTEMI to STEMI, while it had increasing trend upon stabilized condition; the admission level of UII had no correlation to inflammatory marker hs-CRP and ventricular overload marker NT-proBNP. UII is not only related to the extent of atherosclerosis, but also related to the nature of atherosclerosis or the stability of plaques.

Effects of UⅡ/UT system on the expression of inflammatory signal molecules p38 MAPK and NF-κB in LPS-stimulated Kupffer cells / 中华微生物学和免疫学杂志

Objective To investigate the effects of urotensin Ⅱ/urotensin Ⅱreceptor ( UⅡ/UT) system on the expression of inflammatory signal molecules p 38 mitogen-activated protein kinase ( p38 MAPK) and nuclear factor-κB ( NF-κB ) in lipopolysaccharide ( LPS )-stimulated Kupffer cells ( KCs ) . Methods Rat KCs were isolated and purified by means of in situ perfusion and density gradient centrifuga-tion.The isolated cells were randomly divided into six treatment groups including group 1:UⅡ(-) urantide (-)LPS(-), group 2:UⅡ(+)urantide(-)LPS(-), group 3: UⅡ(-)urantide(+)LPS(-), group 4:UⅡ(-)urantide(-)LPS(+), group 5:UⅡ(+) urantide(-) LPS(+) and group 6:UⅡ(-)urantide(+) LPS(+) .Western blot assay was performed to detect p 38 MAPK/p-p38 MAPK protein and NF-κB p65 sub-unit.The DNA-binding activity of NF-κB was tested by electrophoretic mobility shift assay (EMSA).Re-sults There was no significant difference with the expression of p 38 MAPK protein in KCs among the six groups (P>0.05).The expression of p65 protein and p-p38 MAPK and the DNA-binding activity of NF-κB were significantly enhanced in LPS-stimulated KCs from groups 4, 5 and 6 in comparison with those in group 1 (P0.05), but that were decreased in group 6 than those in group 4 (all P<0.01).Conclusion UⅡ/UT system participated in the activation of p38 MAPK and NF-κB signaling pathways in LPS-stimulated primary Kupffer cells .

Roles of UⅡ/UT system played in innate immune inflammatory signal pathway TLR4-IRF3 in LPS-stimulated primary Kupffer cells / 中国免疫学杂志

Objecitve:To investigate effects of urotensin Ⅱ( UⅡ)/UT system on innate immune inflammatory signal pathway TLR4-IRF3 in the lipopolysaccharide (LPS)-stimulated Kupffer cells (KCs).Methods: Rat KCs were isolated and cultured.Pro-in-flammatory cytokines including IL-6,IFN-βand IFN-γwere assayed by ELISA in culture supernatant of KCs.Cell surface TLR4 were tested with flow cytometry technique.Expression of IRF3 were tested with real-time PCR and Western blot.Results: Significant increases were showed in IL-6, IFN-βand IFN-γsecretion, TLR4-expressed positive rates and IRF3 mRNA levels in KCs after stimulated by LPS,but were inhibited via urantide pretreatment.In addition,LPS induced upregulation of nuclear IRF3 protein and downregulation of cytoplasm IRF3 protein in KCs,which were blocked by urantide pretreatment.Conclusion:UⅡ/UT system mediates immune inflammatory response in part through activating TLR 4-IRF3 pathway in LPS-stimulated KCs.

Expression change of serum HCY,UⅡ,ACE and NT-proBNP in essential hypertension patients / 国际检验医学杂志

Objective To study the relationship between essential hypertension(EH)with serum homocysteine(HCY),uroten-sinⅡ(UⅡ),angiotensin converting enzyme(ACE)and N-terminal pro-brain natriuretic peptide(NT-proBNP).Methods By collec-ting the clinical cases,UⅡwas determined by ELISA and HCY,ACE and NT-proBNP were simultaneously detected by ELISA.The detection results were analyzed and compared between the patients with essential hypertension(EH group)and the healthy con-trols.Results The levels of serum HCY,UⅡ,ACE and NT-proBNP in the EH group were significantly increased compared with the healthy control group;the area under curve (AUC)of serum HCY,UⅡ,ACE and NT-proBNP in the ROC curve in the EH group were 0.93,0.765,0.792 and 0.972 respectively,which showed clinical diagnostic significance.Conclusion The levels of HCY,UⅡ,ACE and NT-proBNP are highly expressed in EH and have significant differences compared with the healthy popula-tion,which has the diagnostic value to EH.

Effects of urotensin Ⅱ on the expression of type Ⅰ collagen in human skin fibroblasts / 中华皮肤科杂志

Objective To evaluate the effect of a vasoactive substance urotensin Ⅱ on the expression of type Ⅰ collagen and migration of human skin fibroblasts,and to explore the underlying mechanisms of signal transduction.Methods Fibroblasts were isolated from human foreskin tissues and subjected to primary culture.After a series of subculture,fibroblasts were classified into several groups to be treated with different concentrations (10-10 to 10-6 mol/L) of urotensin lⅡ for 24 hours,urotensin Ⅱ of 10-s mol/L for different durations (0,4,12,24 hours),or pretreated with PD98059 (a mitogen-activated protein kinase kinase inhibitor),nicardipine (a calcium channel blocker) and ciclosporin (a calcineurin inhibitor) of 10-5 mol/L respectively for 30 minutes followed by treatment with urotensin Ⅱ of 10-8 mol/L for 24 hours.The cells receiving no treatment served as the control.Subsequently,enzyme-linked immunosorbent assay was performed to determine the level of urotensin Ⅱ in the supernatant of fibroblasts,and Transwell assay to estimate the migration activity of fibroblasts.Statistical analysis was carried out by t test and analysis of variance.Results Urotensin Ⅱ promoted the expression of type Ⅰ collagen in a time-and concentrationdependent manner.The level of type Ⅰ collagen was increased by 21.2％ (P ＞ 0.05),52.2％ (P ＜ 0.05),84.4％ (P ＜0.05),83.6％ (P ＜ 0.05) and 77.1％ (P ＜ 0.05) in the supernatant of fibroblasts treated with 10-10,10-9,10-8,10-7 and 10-6 mol/L of urotensin Ⅱ for 24 hours respectively,by 23.2％ (P ＞ 0.05),69.5％ (P ＜ 0.05) and 84.1％ (P ＜0.05) in the supernatant of fibroblasts treated with urotensin Ⅱ of 10-8 mol/L for 4,12 and 24 hours respectively,compared with the untreated control fibroblasts.The migration activity was markedly enhanced in fibroblasts treated with urotensin Ⅱ of 10-8 mol/L for 24 hours compared with the control fibroblasts (P ＜ 0.05).PD98059,nicardipine and cyclosporin A inhibited the secretion of type Ⅰ collagen by 18.2％,15.9％ and 19.7％ respectively,and suppressed the migration of fibroblasts by 38.3％ (P ＜ 0.05),20.7％ (P ＜ 0.05) and 81.4％ (P ＜ 0.05) respectively in the groups receiving pretreatment compared with those treated with urotensin Ⅱ alone.Conclusions Urotensin Ⅱ can promote the secretion of type Ⅰ collagen by and migration of fibroblasts,which may be realized through the Ca2+,calmodulin kinase,and mitogen-activated protein kinase pathways.

Inhibitory Effect of an Urotensin II Receptor Antagonist on Proinflammatory Activation Induced by Urotensin II in Human Vascular Endothelial Cells

In this study, we investigated the effects of a selective urotensin II (UII) receptor antagonist, SB-657510, on the inflammatory response induced by UII in human umbilical vein endothelial cells (EA.hy926) and human monocytes (U937). UII induced inflammatory activation of endothelial cells through expression of proinflammatory cytokines (IL-1beta and IL-6), adhesion molecules (VCAM-1), and tissue factor (TF), which facilitates the adhesion of monocytes to EA.hy926 cells. Treatment with SB-657510 significantly inhibited UII-induced expression of IL-1beta, IL-6, and VCAM-1 in EA.hy926 cells. Further, SB-657510 dramatically blocked the UII-induced increase in adhesion between U937 and EA.hy926 cells. In addition, SB-657510 remarkably reduced UII-induced expression of TF in EA.hy926 cells. Taken together, our results demonstrate that the UII antagonist SB-657510 decreases the progression of inflammation induced by UII in endothelial cells.

Effect of budesonide on the expression of urotensin-II and its mRNA in asthma airway remodeling rats / 中国药学杂志

OBJECTIVE: To study the effects of budesonide(BUD) on the expression of urotensin-II (UII) and its mRNA in asthma airway remodeling rats. METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly divided into three groups: the control group, asthma group and BUD treated group. In the experiment, the models of asthma were established by sensitization and challenge with ovalbumin (OVA). The total brochial wall thickness (Wat) and the airway smooth musle thickness (Wam) were measured by image analysis system. The levels of UII in BALF and serum were measured by enzyme linked immunosorbent assay (ELISA). The protein and mRNA expression of UII were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR), respectively. RESULTS: Wat and Warn of of asthma group were significantly higher than those of the control group (P < 0.01, respectively). Compared with asthma group, those were all markedly decreased in BUD group (P < 0.01, respectively). The levels of UII in BALF and serum of asthma group were markedly higher than those in control group and BUD group (P < 0.01, respectively). Immunohistochemistry and RT-PCR showed that the protein and mRNA expression of UII in asthma group were significantly higher than those of control group (P < 0.01, respectively). While those of BUD group were significantly lower than those of asthma group(P < 0.01, respectively). There were a significantly positive correlation between Wat and the protein and mRNA expression of UII. At the same time, there were a significantly positive correlation between Warn and the protein and mRNA expression of UII. CONCLUSION: The beneficial effect of glucocorticoid (BUD) on asthma airway remodeling may be at least in part due to their direct inhibitory effect on UII. Copyright 2012 by the Chinese Pharmaceutical Association.

Expression and clinical significance of urotensin Ⅱ in lung cancer tissue / 国际肿瘤学杂志

ObjectiveTo investigate the expression of urotensin Ⅱ(UⅡ) in the lung cancer tissue from surgical resection of lung cancer patients,and to detect the relationship between UⅡ expression and pathologie types and the clinical stages of lung cancer.MethodsThe expression rates of UⅡof 45 lung cancer tissues and 20 inflammatory pseudotumor were measured by immunohistochemical assay,and the relationship between UⅡ expression and the pathologic types and clinical stages of lung cancer was analyzed.ResultsUⅡwas mainly distributed in lung cancer cell cytoplasm,which was tan-yellow particles.The positive expression rate of UⅡin nonsmall cell lung cancer was 61.3％ (19/31),which was higher than that in small cell lung cancer(7.1％,1/14)and pulmonary inflammatory pseudotumor( 15.0％,3/20) (P ＜ 0.01 ).The positive expression rate of UⅡ was 100％ in adenocareinoma.The positive expression rate of UⅡin staging Ⅲ non-small cell lung cancer( 85.7％ )was higher than that of staging Ⅰ ( 16.7％ ) ( P ＜ 0.05).ConclusionUⅡ cxists in the cytoplasm of lung cancer cells,and the expression of UⅡis correlated with the pathological type and TNM staging of lung cancer.

Correlation between plasma levels of urotensin Ⅱ and severity of liver fibrosis in CCl4 rats / 国际外科学杂志

Objective To examine the correlation between urotensin Ⅱ (UⅡ) concentration and the severity of liver fibrosis. Methods Liver fibrosis model was induced in rats by intraperitoneal administration of CCl4. At 4,6,8 weeks, the rats were sacrificed, and the hepatic tissue hydroxyproline (HYP) content was measured. Hepatic tissue specimens were histopathologically evaluated according to a fibrosis scoring system. Plasma UⅡ levels were measured by ELISA method. Results Plasma UⅡ gradually increased with the increase of duration of CCL4, UⅡ concentration correlated to liver fibrosis ( R2 = 0.875, P ＜ 0.05) and hepatic HYP( R2 = 0.65, P ＜0.05). Conclusion UⅡ was involved in the pathogenesis of liver fibrosis.