Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the human heart, we have previously shown the predominance of endothelin (ET) ETA receptors, in addition to the presence of ET-1, ET-2, ET-3, and big ET-1. ET-1 is a potent constrictor of isolated epicardial coronary arteries, and this action is mediated via ETA receptors. To determine the source of ET in the heart, our aims were to obtain cell cultures from human left ventricle, identify the cell type, and characterize ET secretion and receptor expression. We explanted human left ventricular tissue. Positive staining with alpha-actin antibodies confirmed the presence of smooth-muscle cells, whereas negative staining for sarcomeric actin and von Willebrand factor indicated an absence of cardiac myocytes and endothelial cells, respectively. Therefore, the cultures were identified as human left ventricular smooth-muscle cells (HLVSMCs). Because blood vessels were not macroscopically visible in the ventricular tissue, the HLVSMCs most likely originated from intramyocardial resistance vessels. The cells secreted immunoreactive mature ET and big ET-1 (102 +/- 29 and 73 +/- 10 pM/24 h, respectively; mean of three individuals +/- SEM). Saturation binding studies showed that [125I]ET-1 bind with high affinity in this preparation (Kd 0.21 +/- 0.06 nM; Bmax 15 +/- 4 fmol/mg protein; mean of three individuals +/- SEM). A competition binding study using the ETA-selective antagonist FR139317 (10 pM-10 microM) revealed the predominance of ETA receptors (Kd 0.33 +/- 0.10 nM, n = 3). We have shown that smooth-muscle cells isolated from human left ventricle secrete immunoreactive mature ET and big ET-1, and express mainly ETA receptors. These cells may provide a useful model for studying the effects of ET in the regulation of vascular tone and of the blood supply in the myocardium.
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PMID:Delineation of endothelin receptors in human left ventricular smooth-muscle cells. 858 13

Endothelium-dependent responses are depressed in coronary and peripheral blood vessels after the onset of pacing-induced heart failure in dogs and heart failure of various etiologies in humans. The present study was designed to examine whether these responses were due to decreases in the expression of endothelial cell NO synthase (ecNOS) and cyclooxygenase-1 (COX-1). After 1 month of left ventricular pacing, 8 mongrel dogs were monitored for heart failure as defined by clinical signs and left ventricular end diastolic pressures > 25 mm Hg. Total RNA and protein were isolated from endothelial cells scraped from the thoracic aorta and analyzed by Northern and Western blotting, respectively. Blots probed with 32P-labeled cDNAs for ecNOS and COX-1 were quantified densitometrically, and results were normalized against GAPDH or von Willebrand factor (vWF). In arbitrary units, the ratios of ecNOS to GAPDH were 2.66 +/- 0.77 (mean +/- SEM, n = 17) and 1.12 +/- 0.37 (n = 6 and the ratios of COX-1 to GAPDH were 1.52 +/- 0.52 and 0.56 +/- 0.15 before and after heart failure, respectively. These represent 56% to 64% (P < .05) reductions in ecNOS and COX-1 gene expression. There was no change in the ratios of either COX-1 or ecNOS to vWF. There was also a marked reduction in ecNOS protein after heart failure, estimated at 70%. A marked reduction in nitrite production, a measure of enzyme activity, from thoracic aortas in response to stimulation by either acetylcholine or bradykinin also occurred. To determine whether ecNOS and COX-1 could be independently regulated, an orally active NO-releasing agent, CAS 936, was given to 7 normal dogs for 7 days, and aortic ecNOS and COX-1 mRNAs were analyzed. The ratio of ecNOS to GAPDH was depressed by 52% (P < .05) in aortas from these dogs, whereas the ratio of COX-1 to GAPDH was unchanged. Similar results were found when data were normalized to vWF. These results suggest that at least two endothelial vasodilator gene products are reduced in heart failure, as opposed to a selective defect in NO synthase gene expression.
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PMID:Reduced gene expression of vascular endothelial NO synthase and cyclooxygenase-1 in heart failure. 860 6

Bleeding and platelet dysfunction are prominent features of uremia. Sh ear-induced platelet aggregation (SIPA) involves the interaction of von Willebrand factor (vWF) with platelet membrane glycoproteins (GP) Ib and IIb-IIIa, the same receptor-ligand pair involved in in vivo adhesion and aggregation of platelets in the arterial circulation. We have used a modified rotational cone-plate viscometer to measure SIPA and calcium flux in platelets. Flow cytometric analysis of the surface expression of GP Ib and IIb-IIIa was performed using flourescein isothiocyanate-conjugated monoclonal antibodies CD42b and CD41a, respectively. Uremic patients showed decreased SIPA (controls, 43% +/- 2% [mean +/- SEM]; chronic renal failure patients, 36% +/- 3%; chronic hemodialysis patients, 26% +/- 2%; P < 0.001) along with a decrease in GP IIb-IIIa (controls, chronic renal failure patients, and chronic hemodialysis patients, 840 +/- 25, 649 +/- 42, 661 +/- 38 mean flourescence intensity, respectively; P < 0.0001). Glycoprotein Ib in uremic patients was not significantly different from normal. Chronic hemodialysis patients also demonstrated increased platelet-bound fibrinogen (P < 0.001) and platelet-bound vWF (p < 0.01). Calcium flux and thromboxane B(2) generation during SIPA of uremic platelets was normal. However, uremic plasma showed twice the normal concentration of vWF (P < 0.001) and sodium dodecyl sulfate agarose gel electrophoresis revealed the presence of fibrinogen fragments. Mixing experiments demonstrated an inhibitory effect of uremic plasma on SIPA of normal platelets (decreased from 39% +/- 3% at baseline to 31% +/- 3% after incubation in uremic plasma) along with an activation-independent increase in platelet-bound fibrinogen and platelet-bound vWF. When uremic platelets were incubated in normal plasma, their SIPA increased from 12% +/- 5% at baseline to 18% +/- 4% after incubation in normal plasma; (P = 0.002), although it did not return to normal. These results suggest that the uremic platelet dysfunction results from decreased GP IIb-IIa availability due to receptor occupancy by fibrinogen fragments (and possibly vWF fragments).
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PMID:Uremic patients have decreased shear-induced platelet aggregation mediated by decreased availability of glycoprotein IIb-IIIa receptors. 860 4

Classically, primordial follicles have flattened pre-granulosa cells that become cuboidal and divide during follicular activation. This change in shape is thus an index of activation. To examine this and follicular morphology in cattle, ovaries were processed for light and electron microscopy (n = 21). In single sections (5 microns thick), primordial follicles had a mean ratio of maximum to minimum diameters of 1.33 +/- 0.18 (mean +/- SD; n = 317, randomly selected), indicating that they had a prolate rather than a spherical shape. The prolate shape was attributable to clustering of granulosa cells at two opposite poles on the long axis of each follicle; and in each histological section, 82.5% of primordial follicles (n = 317) had at least one cuboidal granulosa cell. More accurate measurements of primordial follicles indicated that they had three dimensions measured as length (45.4 +/- 2.4 microns), breadth (26.8 +/- 1.5 microns), and depth (< 30.4 +/- 1.4 microns) (mean +/- SEM; n = 12, constructed from serial sections); a surface area of 0.0032 mm2; and 24 +/- 2 granulosa cells. The ultrastructural morphology of the cells of the bovine primordial follicle (n = 31 examined by electron microscopy) was similar to that of other species. The ovarian cortex was composed of discrete zones. The zones containing primordial follicles were substantially avascular, as observed by localizing von Willebrand factor, and rich in collagen fibrils. In conclusion, since primordial follicles of bovine ovaries contain some cuboidal pre-granulosa cells, changes in shape cannot be used with certainty as a marker of activation of bovine follicles.
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PMID:Morphological characterization of bovine primordial follicles and their environment in vivo. 890 10

Whether the serum levels of endothelin, a vasoconstrictive peptide produced in the endothelial cell, increase in preeclamptic patients is still controversial. We performed immunohistochemical studies to observe the changes in endothelin-1 (ET-1) in preeclamptic kidney tissues. The monoclonal anti-human ET-1 antibody (Yamasa, Japan) and anti-von Willebrand factor (vWF, Dako, Denmark), a marker of endothelial cells, were used for the studies by the strepto-avidin-biotin peroxidase method (ABC-POD Kit, Wako, Japan). Twenty-nine patients and 12 normal controls were divided into four groups. The preeclamptic group included 14 patients diagnosed with preeclampsia by clinical symptoms of hypertension, proteinuria, and edema occurring in late pregnancy and as having preeclamptic nephropathy. They underwent renal biopsy 16.7 +/- 1.0 (mean +/- SEM) days after delivery. The nephrotic group comprised 10 normotensive nonpregnant patients with nephrotic-range proteinuria examined through biopsy before treatment (six cases of minimal change, two of focal segmental glomerulosclerosis, one of membranous nephropathy, and one of IgA nephropathy). The pregnant women with preexisting glomerular disease group included five pregnant women with normal renal function who were normotensive and had no increase in the amount of proteinuria throughout pregnancy. They underwent renal biopsy 10.8 +/- 2.9 days after delivery (two cases of membranous nephropathy, one of focal segmental glomerulosclerosis, one of thin basement membrane disease, and one of non-IgA mesangioproliferative glomerulonephritis). The normal kidney group comprised 12 healthy tissue samples taken from nephrectomized kidneys (five cases of renal cell carcinoma, one case of lipofibrosarcoma, and six cases of kidney transplant donors). In these four groups, ET-1 and vWF showed equally positive staining in small arteries. VWF also showed positive staining in arterioles and peritubular capillaries in all groups. Although the glomeruli showed positive staining with ET-1 along the capillary walls in the normal group and the nonpregnant nephrotic group, they showed very weak or negative results in the preeclamptic group. Moreover, gravida with underlying glomerular disease without superimposed preeclampsia also showed negative findings of ET-1 in the glomeruli. The glomeruli in the four groups showed positive findings, with vWF readings the same as in the controls. These results indicate that the production of ET-1 in the glomerular endothelial cells decreases in cases of both preeclampsia and normal pregnancy, and the condition may be caused by pregnancy itself.
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PMID:Immunohistochemical study of endothelin-1 in preeclamptic nephropathy. 904 Dec 9

Endothelial dysfunction is a prevalent phenomenon in non-insulin dependent diabetic (NIDDM) patients with hypertension and albuminuria, and may contribute to the development and progression of cardiovascular disease, which is the main cause of the high morbidity and mortality observed in these patients. Therefore the aim of our study was to evaluate whether inhibition of angiotensin-converting enzyme (with lisinopril 10-20 mg day-1) could ameliorate endothelial dysfunction more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg day-1), usually in combination with a diuretic. We performed a 12-month prospective, randomized, double-blind, parallel study in 43 hypertensive NIDDM patients with diabetic nephropathy (21 treated with lisinopril and 22 with atenolol). The following variables were measured: 24-h ambulatory blood pressure (ABP); transcapillary escape rate of albumin (TERalb; i.e. initial disappearance of intravenously injected 125I-labelled human serum albumin); serum concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16 atenolol; age 60 years, SD 8; 25 males) out of 35 who completed the study and had valid measurements of TERalb. At baseline the two groups were comparable; TERalb (8.5 (SEM 0.6) vs. 7.2 (0.4)%); vWF (2.09 (range 0.82-4.34) vs. 1.97 (0.95-3.86) IU ml-1; UAE 916 (x/divided by antilog SEM 1.3) vs. 1444 (1.2), and mean ABP 110 (SEM 3) vs. 113 (2) mmHg, in the lisinopril and atenolol group, respectively. During follow up, the mean ABP was equally reduced in the lisinopril and atenolol group, by 12 (SEM 2) vs. 10 (2) mmHg, respectively, TERalb decreased in the lisinopril group by 0.6 (SEM 0.7)%, whereas it increased in the atenolol group 1.5 (0.5)%; the mean difference was 2.2% (95% CI, 0.5 to 3.9; p = 0.015). UAE was reduced by 45% (95% CI, 25 to 60) in the lisinopril group vs. 10% (-15 to 30) in the atenolol group (p = 0.014). Serum vWF was not changed during follow up in either group. Our study suggests that lisinopril has both reno- and vasculoprotective properties in hypertensive NIDDM patients with diabetic nephropathy.
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PMID:Lisinopril improves endothelial dysfunction in hypertensive NIDDM subjects with diabetic nephropathy. 927 69

Cardiopulmonary bypass (CPB) causes activation of cascade systems. Although heparin coating of CPB circuits improves biocompatibility, the effects on coagulation remain controversial. Theoretically, heparin coating should permit the reduction of systemic anticoagulation during CPB. We investigated influences on haemostatic variables in animal CPB, comparing heparin-coated circuits and reduced systemic heparinization (group HC) with uncoated circuits and full heparinization (group C). Twenty pigs underwent 2-h CPB. Seven (HC, n = 4; C, n = 3) were weaned from CPB and studied for up to 4 h. Total administered heparin was 470 +/- 6 IU/kg (mean +/- SEM) in group C and 100 +/- 0 IU/kg in group HC. Protamine dosage was significantly reduced in group HC. In group C, levels of prothrombin complex, factor VIII and adhesive platelets were reduced significantly during CPB, and postoperatively there were significantly lower values of prothrombin complex, fibrinogen, antithrombin III, factor VIII and adhesive platelets but a significantly increased concentration of von Willebrand factor and cumulative bleeding after 4 h. In conclusion, heparin-coated CPB circuits combined with lowered heparin dosage reduced coagulation factor consumption and preserved platelet function, possibly contributing to improved postoperative haemostasis.
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PMID:Haemostasis at low heparin dosage during cardiopulmonary bypass with heparin-coated circuits in pigs. 949 31

Cardiopulmonary bypass (CPB) causes activation of cascade systems. Although heparin coating of CPB circuits improves biocompatibility, the effects on coagulation remain controversial. Theoretically, heparin coating should permit the reduction of systemic anticoagulation during CPB. We investigated influences on haemostatic variables in animal CPB, comparing heparin-coated circuits and reduced systemic heparinization (group HC) with uncoated circuits and full heparinization (group C). Twenty pigs underwent 2-h CPB. Seven (HC, n = 4; C, n = 3) were weaned from CPB and studied for up to 4 h. Total administered heparin was 470 +/- 6 IU/kg (mean +/- SEM) in group C and 100 +/- 0 IU/kg in group HC. Protamine dosage was significantly reduced in group HC. In group C, levels of prothrombin complex, factor VIII and adhesive platelets were reduced significantly during CPB, and postoperatively there were significantly lower values of prothrombin complex, fibrinogen antithrombin III, factor VIII and adhesive platelets but a significantly increased concentration of von Willebrand factor and cumulative bleeding after 4 h. In conclusion, heparin-coated CPB circuits combined with lowered heparin dosage reduced coagulation factor consumption and preserved platelet function, possibly contributing to improved postoperative haemostasis.
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PMID:Haemostasis at low heparin dosage during cardiopulmonary bypass with heparin-coated circuits in pigs. 940 94

Ionizing irradiation has been shown to induce an increased release of von Willebrand factor (vWF) in human endothelial cells in vitro. The present study was undertaken to investigate whether an increase in expression of vWF also occurs in glomerular endothelial cells in vivo after irradiation of the kidney. Increased expression of vWF may initiate prothrombotic changes, and the resultant vascular damage could cause renal failure. The amount of adherent leukocytes in the renal cortex after irradiation was also quantified, since this may contribute to the histological changes that occur after irradiation. Changes in expression of glomerular vWF and in the amount of leukocytes were related to the development of impairment of renal function, as assessed with the [51Cr]EDTA retention assay. Mice were given bilateral irradiation (single dose of 16 Gy) or were sham-irradiated and were sacrificed at intervals of 1 day to 40 weeks after irradiation. Immunohistochemical analysis of kidney cryosections was performed using a polyclonal vWF antibody or monoclonal CD45 antibody (leukocyte common antigen). The amount of glomerular vWF staining and CD45 staining in the renal cortex (percentage surface coverage) was quantified using a computerized image analyzer. The mean glomerular vWF staining in the nonirradiated kidneys was 34.4 +/- 6.2% (mean +/- SEM, 10 weeks after sham treatment). After irradiation, the expression of glomerular vWF increased gradually from 10 weeks to 53.4 +/- 3.6% at 40 weeks. The total number of leukocytes in the renal cortex of nonirradiated mice at 10 weeks after sham treatment was low, with a mean area of 1.0 +/- 0.09%, whereas in the irradiated kidneys the relative tissue area covered by leukocytes increased to 7.6 +/- 2.1% at 40 weeks. These alterations preceded impairment of renal function. The extent to which these changes are causally related to impairment of function will be the subject of future study using specific antithrombotic and anti-inflammatory agents.
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PMID:Increased expression of glomerular von Willebrand factor after irradiation of the mouse kidney. 980 94

The purpose of this study was to determine whether plasma von Willebrand factor concentrations are correlated with the degree of intestinal ischaemia-reperfusion injury. Forty-six anaesthetised adult Wistar rats were divided into five groups. The sham-operated group (S, n=10) had laparotomy and isolation of the superior mesenteric artery without clamping. Three ischaemia-reperfusion groups (n=10 in each) had clamping of the superior mesenteric artery for 15, 30, and 45 minutes, respectively, and reperfusion for 15 minutes. A control group (C, n=6) had direct puncture of the heart to sample blood. Mean arterial pressure was measured continuously. Blood was collected at the end of the study to measure von Willebrand factor. The small bowel injury was graded histologically. There was a significant systemic hypotension after declamping in all ischaemia-reperfusion groups, which had a high negative correlation with the histological score (R=-0.46, F=10.1, p<0.003, simple linear regression). Plasma von Willebrand factor was significantly elevated in the three ischaemia-reperfusion groups compared with the control group but not significantly different from the sham-operated group (mean von Willebrand factor concentration (SEM): 156 (29), 283 (29), 295 (25), 381 (44), and 366 (40)% in C, S, ischaemia-reperfusion 15, ischaemia-reperfusion 30, and ischaemia-reperfusion 45 groups, respectively). The concentration of von Willebrand factor was not correlated to the histological score (R=0.22, F=1.83, p<0.2) or the degree of hypotension after the removal of the clamp (R=-0.22, F=1.8, p<0.2, simple linear regression). This study shows that von Willebrand factor concentration does not correlate with the degree of intestinal ischaemia-reperfusion injury. It is unlikely that von Willebrand factor can be used as a predictor of disease severity.
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PMID:Plasma von Willebrand factor and intestinal ischaemia-reperfusion injury in rats. 1039 Jan 30


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