The present study, using the different catecholamines, observed the effects on plasminogen activator (PA) activity release in the vascular wall of rat hindlegs. The results showed that adrenaline perfusion induced the highest PA activity in three different catecholamines. Propranolol completely blocked PA activity induced by isoprenaline. PA activity induced by adrenaline or noradrenaline was completely inhibited by propranolol combined with phentolamine. During physiological stress the increase of plasma noradrenaline level was accompanied with higher PA activity. These data indicated that exogenous catecholamines produced a increase of PA activity via ?-adrenoreceptors stimulation mainly, as well as ?-receptors partially. The endogenous increase of catecholamines showed the same effect on fibrinolytie system.

AIM: To investigate the influence of tumor necrosis factor ?(TNF ?) or angiotensin Ⅱ(Ang Ⅱ) on tissue factor(TF) gene expression and the regulatory effect of upstream sequence on TNF ? or Ang Ⅱ-induced TF gene transcription in human vascular endothelial cells.METHODS: TF mRNA in endothelial cells was analyzed by in situ hybridization. By means of gene recombinant technique, we constructed two luciferase reporter genes containing different upstream sequence of TF gene. The two luciferase reporter genes, together with the intracontrol plasmid pSV-?-gal were co-transfected respectively into cultured human vascular endothelial cells. The relative luciferase activities were detected.RESULTS: TNF? or Ang Ⅱ could increase the expression of TF mRNA in vascular endothelial cells. TNF? and AngⅡ could significantly increase the luciferase expression in the p-244/+121bp Luc transfected endothelial cells, respectively. The luciferase expression in the p-111/+121bp Luc transfected endothelial cells decreased significantly compared with that in the p-244/+121 bp Luc transfected endothelial cells and there was no significant difference compared with control group. CONCLUSION: Upstream sequence p-244/-112bp of TF gene may play an important regulatory role in TNF ? or AngⅡ-induced TF gene expression in human vascular endothelial cells.

BACKGROUND:α-zearalanol, a natural phytoestrogen has the effect of anti- atherosclerosis like the estrogen but with less side effect. Therefore, it has a potential for more application in the future. OBJECTIVE: To investigate the effect of 17β-estradiol (E2) and α-zearalanol (ZAL) on coagulation and fibrinolysis in ovariectomized rats and to compare and analyze their effects. DESIGN: An observational and controlled experiment. SETTING:Department of Pathophysiology of the Capital University of Medical Sciences and the Department of Pathophsiology of the Institute of Basic Medical Sciences of Chinese Academy of Medical Sciences and Peking Union Medical College. MATERIALS: The experiment was completed at the Science Department of Experiment Animals from July to September 2003. Thirty-six healthy female Wistar rats aged 12-week old , weighing (250±10)g, clean grade were involved. The animals were divided into 4 groups, namely sham-operation control group, ovariectomy (OVX) group, OVX +E2 group, OVX+ZAL group with 9 rats in each group. METHODS: For the rats in the sham-operation control group, operation was performed without removing the ovary. For the rats in the OVX group,ovariectomy was performed and the rat models were made at the sterile condition. 1 mg/kg 17β-estradiol and 1mg/kg α-zearalanol were respectively injected intramuscularly into the rats in the OVX +E2 group and OVX+ZAL group 14 days after the operation, once every three days for 35days altogether. After the administration of 17β-estradiol or α-zearalanol for 5 weeks, rats were killed, and blood was collected through the common carotid artery and plasma was collected from it. The prothrombin time (PT)and the activated partial thromboplastin time (APTT) were determined with coagulation method. The level of fibrinogen (FG) was measured with an automatic biochemistry analyzer. Tissue factor(TF)level was determined with ELISA method, the activity of tissue plasminogen activator(t-PA)and plasminogen activator inhibitor type 1 (PAI-1)were determined with chromogenic substrate assay. At the same time, the uteri were cut off and weighed by an electronic scale to work out the uteri weight/body weight (g/kg). MAIN OUTCOME MEASURES: ① PT, APTT, FG,TF, t-PA, PAI-1; ②uteri mass/body mass RESULTS: All the 36 rats entered the stage of the result analysis. ①change of PT: it was shorter in the OVX group than that in the sham-operation control group (P ＜ 0.01 ), but it was longer than that in the OVX group after supplementation of E2 and ZAL (P ＜ 0.05-0.01 ). ② Change of FG and TF: they were significantly higher than those in the sham-operation control group (P ＜ 0.05-0.01 ). But, they were lower than those in the OVX group after supplementation of E2 and ZAL (P＜ 0.05-0.01 ). ③Change of tPA: It was significantly lower in the OVX group than that in the sham-operation control group [(0.33±0.33) μkat/L,(4.00±1.50) μkat/L,(q=9.43, P ＜ 0.01 )]. However, it was significantly higher than that in the OVX group after supplementation of E2 and ZAL [(1.83 ±0.67)μkat/L,(1.17±0.83) μkat/L, (q=13.50, P ＜ 0.01; q=5.00, P ＜ 0.05). ④ Change of PAI-1: It was significantly higher than that in the sham-operation control group [(2.33±0.67) μkat/L,(1.17±0.33) μkat/L,(q=10.5, P ＜ 0.01 )]. ⑤Uteri mass/body mass: It was significantly lower in the OYX +ZAL group than that in the OVX+ E2 group [0.66,1.96, (q=14.67, P ＜ 0.01)]. CONCLUSION: Both 17β-estradiol and α-zearalanol can resume the balance of coagulation-fibrinolysis of ovariectomized rats, suggesting that αzearalanol has a similar protective effect similar to that of 17β-estradiol on cardiovascular system. As α-zearalanol has less adverse effect on uteri enlarging than 17β-estradiol, it has a better prospect for substitution of estrogens as a natural phytoestrogen.

Pulmonary artery hypertension is a serious disease in respiratory system and a key tache in the mechanism of pulmonary-heart disease. The pathological changes include the contraction and remodeling of the pulmonary vessels. There are more and more studies on the pulmonary artery hypertension because of its refractory character and the following increasing mortality. This article summarizes the updating research of the factors and mechanism studied on pulmonary artery hypertension recently, to provide a new view for the clinical and basic medical investigation.

AIM: To explore the role of adrenomedullin (AM) in tissue factor (TF) and TFPI expression in HUVECs stimulated with oxLDL and to investigate its possible signal transduction pathway. METHODS: Using chromogenic assay and RT-PCR technique, TF and TFPI protein activity and mRNA level in cultured HUVECs were observed. The signal transduction pathway of AM action was further analyzed by applying Rp-cAMP (cAMP antagonist), PD098059 (MAPK inhibitor) and H7 (PKC inhibitor). RESULTS: AM inhibited TF protein activity and mRNA expression in HUVECs treated with oxLDL in a concentration-dependent fashion; AM alone increased TFPI protein activity and mRNA expression in concentration-dependent and time-dependent manner. Moreover, AM reversed the decrease in TFPI protein activity and mRNA level caused by oxLDL; AM-induced TFPI expression was inhibited by cAMP and MAPK inhibitors. CONCLUSION: AM can reverse the effects of oxLDL on TF and TFPI expression in HUVECs, which can help improve the state of blood coagulation in atherosclerosis and delay development of atherosclerosis.

BACKGROUND: It is commonly thought that the expression of tissue factor (TF) gene in human umbilical vein endothelial cells (HUVECs) could be induced by tumor necrosis factor(TNF-α) . But the intervention effect of monomer extract of radix salviae miltiorrhizae(764-3) on TF expression in duced by TNF-α in endothelial cells has not been reported and the mechanism is still unclear.OBJECTIVE: To investigate the intervention effect of 764 - 3 on TF expression and calcium ion( [Ca2+] i) induced by TNF-α in HUVECs so as to probe into the possible mechanism of 764 - 3 for preventing cardiovascular thromboembolic diseaseDESIGN: Randomized and controlled trial.SETTING: Laboratory of Department of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College MATERIALS: This study was conducted in the Department of Pathophysiology, Institute of Basic Medical Science, Peking Union Medical College,Chinese Academy of Medical Sciences from May 1998 to September 1999. Umbilical cord was chosen from Beijing Obstetrics and Gynecology Hospital.INTERVENTIONS: ECV304 cell strain and HUVECs were cultured in vitro. With gene recombination techniques, two luciferase reporter genes containing different length of human TF gene promoter were constructed. The two-luciferase reporter genes, together with the intracontrol plasmid pSV-3-gal were respectively cotransfected into cultured ECV304 and HUVECs.MAIN OUTCOME MEASURES: The activities of luciferase and βgalactosidase were detected in ECV304 and HUVECs treated by TNF-α or/and 764 -3. Taking Fluo- 3/AM as fluorescent indicator, [Ca2+]i in single HUVEC was observed with laser-scanning confocal microscope.RESULTS: The luciferase expression in the p - 244/ + 121 bp luc transfected endothelial cells was significantly increased when the cells were exposed to 100 U/mL TNF-α. The induction of TNF-α could be inhibited by 764 -3 ( P ＜ 0.05). The luciferaseexpression in the p - 111/+ 121 bp Luc transfected endothelial cells was significantly lower than that in the p - 244/+ 121 bp ones and at the same time, 764 -3 did not cause the significantly change of the luciferase expression. Under laser-scanning confocal microscope, TNF-α increased [Ca2 +] i in single HUVEC, but the effect was inhibited by 764 - 3.CONCLUSION: TF gene expression induced by TNF-α was inhibited by 764 - 3 in endothelial cells, which was dependent on the p-244/+ 121 bp,and [Ca2+ ]; might be involved in it.

Objective To study the pattern of ultrasonic bone mineral density of calcaneus with age, height and body weight, and to establish a normal reference value of stiffness index (SI) of females in Southern China for providing scientific foundation for osteoporotic diagnosis and prevention. Methods SI for calcaneus in 2498 healthy people 10～87 years old was measured with Achilles Express ultrasound apparatus made in USA. They were divided into groups according to sex and age. One group for 10 years each and the records beyond 69 years were classified into one group, total 7 groups. Results The SI showed a characteristic mild rise-then-fall pattern with increasing age. And the peak value of SI presented in 20～29 age group. Pearson correlation analysis showed negative correlation between SI and age and a positive correlation between SI/ height and weight. The prevalence of osteoporosis gradually increase with age. Conclusion There are significant correlations in SI with age, height and weight; the values of SI will provide an important data reference to establish the normal values and diagnostic]standard of osteoporosis.

AIM:To study the changes of ?-adrenoceptors in peripheral lymphocytes at different stages of asthma. METHODS:?-adrenoceptors in peripheral lymphocytes, cAMP and cGMP levels in blood plasma were measured by radioligand binding assay and radioimmunoassay.RESULTS:Bmax and Kd of ?-adrenoceptors in asthma at remission stage were markedly higher than that in normal subjects, while cAMP levels in blood plasma were not different between them. Bmax of ?-adrenoceptors and cAMP levels in blood plasma in asthma at acute exacerbation stage were significantly lower than that in normal subjects, Kds between these two groups were not much different. There was no correlation between ?-adrenoceptors, cAMP and cGMP levels in blood plasma and ventilatory functions.CONCLUSIONS:Changes of ?-adrenoceptors in asthma rather be a pathological change accompanied by the course of the disease than a primary defect.

AIM: To study the influence of minimal modified low density lipoprotein (mmLDL) on plasminogen activator inhibitor-1 (PAI-1) activity, gene expression and regulation in human vascular endothelial cells. METHODS: The PAI-1 activity in human umbilical vein endothelial cells (HUVEC) culture medium was measured by chromogenic assay. The PAI-1 mRNA expression were determined by Northern blot. Using gene recombination techniques, four luciferase reporter gene plasmids containing different length of human PAI-1 gene promoter were constructed. Through the transient transfection analysis, the roles of AP-1 element(from -823 bp to -553 bp) in PAI-1 promoter have been determined. In order to further verify the role of AP-1 element, the three site-directed mutants were received using PCR and sequencing assay. RESULTS: The PAI-1 activity and mRNA level were increased when HUVECs were exposed to 50 mg/L mmLDL. At the same time, the AP-1 protein level was increased in nuclear. The induction by mmLDL were decreased markedly when the three AP-1 elements in PAI-1 promoter had been mutated, respectively. CONCLUSION: (1) mmLDL increased PAI-1 activity and mRNA expression in HUVEC. (2) Increase in PAI-1 activity induced by mmLDL was related to its mRNA expression. (3) Three AP-1 element in PAI-1 promoter may have an important role in PAI-1 gene transcription in endothelial cells induced by mmLDL.

AIM: The study is designed to probe for the relationship between waist to hip ratio(WHR)and static lung volumes of adults. METHODS: In July-October 2008, 1 307 healthy adults(372 males and 935 females)were selected in Heilongjiang province by means of questionnaire and physical examination. The height, weight, WHR, fat mass, percentage body fat and lung function were measured, and then grouped according to the standard of classification of WHR(central obesity male WHR ≥ 0.86, female ≥ 0.82)for analysis of the relationship between WHR and static lung volume. RESULTS: WHR was found, regardless of sex, to tend to go up with the increase in age and BMI(P<0.01), and both the fat mass and percentage body fat of the central obesity group were higher than those in the group with normal WHR(P<0.01). An independent negative correlation was found(P<0.05), also regardless of sex, between the WHR with expiratory reserve volume(ERV)in all these adults. ERV in central obesity group was lower than that in the group with normal WHR(P<0.05). Compared to the normal group, ERV in the central obesity group decreased by 11% for males and 8% for females(P<0.05). However, with regard to the relationship between WHR and VT, IC, MV, and VC, gender differences were found. For the males, a significant independent positive correlation was observed between WHR and IC(P<0.05), with IC of the central obesity group 6% higher than that in the group with normal WHR(P<0.05). For the females, significant independent positive correlation was found between WHR and MV(P<0.05), with the VT and MV of the central obesity group 7% and 6% higher(P<0.05), respectively, than that in the group with normal WHR. CONCLUSION: WHR is in an independent negative correlation with ERV. The elevation of WHR may play a role in the impairment of respiratory function. Its occurrence is accompanied by a rise of IC for the male and a rise of MV for the female. These changes in the two genders could be associated with the decrease in arterial oxygen tension caused by the decrease of ERV.