Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HPMECs were successfully isolated by differential trypsinization from peripheral lung lobes. The cells proliferated rapidly in EGM-MV with 10% FBS and were serially cultivated for more than 20 passages (1:4 split ratio) in vitro. Cells were characterized as endothelial based upon their cobblestone morphology, the presence of factor VIII-related antigen, incorporation of DiI-Ac-LDL, tubule-like structure formation in Matrigel, and positive staining for ACE. Adhesion molecules were tested at passage 3 and passage 12. Cells demonstrated intense staining for PECAM-1 both unstimulated and stimulated with TNF-alpha (20 ng/ml). The adhesion molecules ICAM-1, VCAM-1, ELAM-1, and P-selectin differed in expression on unstimulated cells. ICAM-1 was constitutively expressed on unstimulated cells and the expression was increased by TNF-alpha stimulation (20 hr). In contrast, VCAM-1, ELAM-1, and P-selectin were not detected on unstimulated cells but were detected after stimulation with TNF-alpha. The inducibility of adhesion molecules was different. VCAM-1 (10 hr) and ELAM-1 (4 hr) were expressed more strongly than P-selectin (minutes to 4 hr). The adhesion molecule profile found on passage 12 was the same as on passage 3. CD36 was not detected on both unstimulated and stimulated (4 and 8 hr) cells. The peak of adhesion of HL-60 cells to TNF-alpha activated HPMEC monolayers was around 8 hr. The results indicate that HPMEC can be continuously grown in vitro for many passages without losing their adhesion molecule expression. This expression of adhesion molecules confirms that HPMECs might be a good in vitro model in the understanding of various aspects of pulmonary microvascular endothelial cell function and may be useful as the basis for studies of adhesion molecule targeted therapies of pulmonary inflammatory diseases.
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PMID:Expression of adhesion molecules in cultured human pulmonary microvascular endothelial cells. 858 50

To test the hypothesis that platelet activation is present in hypertension, we measured plasma markers beta thromboglobulin and soluble P-selectin in hypertensive patients and normotensive controls. Both markers were raised in the patients (P < 0.05), and in a subgroup of patients, beta thromboglobulin was reduced with successful treatment of hypertension with the ACE inhibitor quinapril. We suggest that reversible platelet activation is present in hypertension. This may be a contributing factor to the link between this risk factor and the development of thrombotic disease such as stroke.
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PMID:Evidence of platelet activation in hypertension. 936 84

Redox stress during post-ischemic reperfusion may be the prime signal for processes leading to myocardial remodelling and hypertrophy. Nitric oxide (NO) is antioxidative, antiadhesive for neutrophils (PMN) and antiproliferative. Thus, enhancing endothelial production of NO, e.g. by inhibiting breakdown of endogenous bradykinin via angiotensin converting enzyme (ACE), could be beneficial. The effect of cilazaprilat (CILA, 10 micro M), an ACE inhibitor, on redox status, expression of the adhesion molecule P-selectin, and PMN adhesion under conditions of oxidative stress was investigated in cultured human umbilical vein endothelial cells (HUVECs). Incubation of the cells with H2O2 (0.1 and 1 mm) for 15 min served as oxidative stimulus. The intra- and extracellular concentrations of reduced and oxidized glutathione (GSH and GSSG) were measured by HPLC as indicators of endothelial redox status. Expression of P-selectin was measured by flow cytometry. Furthermore, firm leukocyte adhesion to HUVECs was assessed. In controls, the intracellular ratio GSH/GSSG averaged 47 and dropped to 30 after incubation with 0.1 mm H2O2. The ratio declined to 6.5 with 1 mm H2O2. CILA blocked the effects of 0.1 mm H2O2, but was ineffective against 1 mm peroxide. The extracellular ratio did not discriminate between 0.1 and 1 mm H2O2, falling from 18 to 1 in both situations. P-selectin expression rose from 100% (control) to 146% after 1 mm H2O2 without CILA, but only to 114% in the presence of CILA. PMN adhesion was enhanced from about 1600 PMN per microwell (control) to 4300/well by 1 mm H2O2. CILA had no significant effect on adhesion (3900 PMN/well). Exposure of HUVECs to 0.1 mm H2O2 affected neither P-selectin expression nor PMN adhesion. Consequently, ACE inhibition can mitigate mild (0.1 mm H2O2) but not more severe redox stress in HUVECs. Irrespectively, CILA reduced the upregulation of P-selectin at the higher H2O2 concentration, indicating that this process is regulated independently of the cellular redox status. The firm adhesion of PMN to HUVECs was independent of P-selectin expression.
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PMID:Effects of ACE-inhibition on redox status and expression of P-selectin of endothelial cells subjected to oxidative stress. 940 70

We measured serum soluble adhesion molecules levels in patients with sarcoidosis. The serum levels of soluble ICAM-land L-, E-, and P-selectin were significantly elevated in patients with sarcoidosis compared with healthy volunteers. However, there was no significant difference in serum soluble VCAM-1 levels between the patients and healthy volunteers. A significant correlation was observed between serum soluble L-selectin levels and the number of lymphocytes in the bronchoalveolar lavage fluid of patients with sarcoidosis. Although higher levels of serum soluble adhesion molecules were present in accordance with the clinical stage of sarcoidosis, the differences were not statistically significant. There was a significant correlation between serum ACE and soluble ICAM-1 or VCAM-1 levels. These findings suggest that soluble adhesion molecules may play an important role in the pathogenesis of sarcoidosis.
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PMID:[Serum soluble adhesion molecules in patients with sarcoidosis]. 949 44

The placental endothelium contributes to regulating transplacental exchange and maintaining the immunological maternofetal barrier. We characterized the endothelial phenotype in human normal term placentae with a panel of antibodies to endothelial antigens using a standardized immunofluorescence method. Placental endothelium strongly expressed vWF, PAL-E, H-antigen, thrombomodulin, PECAM-1, CD34, CD36, ICAM-1, CD44, thy-1, A10/33-1, VE-cadherin, caveolin-1 and HLA-G, whereas occludin, claudin-1, eNOS, angiotensin converting enzyme (ACE), ICAM-2, endoglin and integrin-alphathetabeta(3)were weakly expressed. PGI(2)synthase, tissue factor, E-selectin and VCAM-1 were not detected. Some antigens were heterogenously expressed along the vascular tree or within individual villi. Expression of ACE, eNOS, vWF, P-selectin, E-selectin, integrin alpha(v)beta(3)and endoglin was stronger in the maternal decidual vessels, while PECAM-1, CD44, thy-1 and caveolin-1 expression was stronger in fetal vessels. Some endothelial markers were present in trophoblasts and stroma. Endothelial proliferation was apparent in mature intermediate and terminal villi. There was limited inflammatory response to TNFalpha in explants, characterized by upregulation of vWF, P-selectin, PECAM-1 and CD44, downregulation of thrombomodulin, but no increase in ICAM-1 expression, nor induction of E-selectin, VCAM-1 or tissue factor. These patterns of heterogeneity, proliferative activity and inflammatory activation may underlie the specific physiological roles of the placental endothelium.
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PMID:Phenotype of the endothelium in the human term placenta. 1116 50

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.
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PMID:Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors. 1214 57

The objective of the investigation was to assess whether circulating adhesion molecules, von Willebrand factor (vWf) and endothelin-1 are elevated in patients with mild uncomplicated essential hypertension without further risk factors of atherosclerosis and whether they could serve as indicators of endothelial dysfunction in this form of hypertension. Furthermore the authors investigated the effect of ACE inhibitor treatment (ACEI), quinapril, on the level of these markers of endothelial dysfunction. The level of adhesion molecules [intercellular cytoadhesion molecule-1 (ICAM-1), E-selectin, P-selectin], von Willebrand s factor (vWf) and endothelin-1 were assessed in patients with mild essential hypertension without further cardiovascular risk factors or clinical manifestations of atherosclerosis before and after quinapril treatment (n = 25) and compared with normotensive controls (n = 29). The results of the examinations provided evidence that contrary to controls the hypertensive subjects had significantly higher ICAM-1 levels (237.8 vs. 207.8 ng/ml, P = 0.02) vWf (118 vs. 106 IU/dl, p < 0.05) and endothelin-1 (5.81 vs. 5.15 fmol/ml, p < 0.05). Three-month treatment of hypertensive patients with ACEI led to a significant drop of endothelin-1 levels (5.81 vs. 5.26 fmol/ml, p = 0.01). The authors proved also an unequivocal declining trend of other cytoadhesion molecules and vWf after ACEI treatment, the changes however were not statistically significant. From the investigation it may be concluded that also patients with uncomplicated essential hypertension without other cardiovascular risk factors or clinical manifestations of atherosclerosis have significantly elevated plasma levels of ICAM-1, vWf and endothelin-1. Higher concentrations of these factors suggest endothelial dysfunction already in mild forms of essential hypertension without further risk factors or cardiovascular complications. A significant drop of endothelin-1 and declining trend of the other investigated indicators suggest that ACEI treatment can favourably influence endothelial dysfunction in hypertensive patients also independently on reduction of the BP.
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PMID:[Is mild essential hypertension without obvious organ complications and risk factors associated with increased levels of circulating markers of endothelial dysfunction? Effect of ACE inhibitor therapy]. 1242 1

The angiotensin-converting enzyme inhibitor (ACE-I) enalapril has been shown to lower elevated levels of circulating adhesion molecules (cAM) in critically ill patients. To delineate the mechanisms of this possibly beneficial effect of enalapril, we studied the acute effects of enalapril in a well-defined model of endotoxin-triggered, cytokine-mediated cAM up-regulation. In a randomized, controlled trial, 30 healthy male volunteers received 2 ng/kg lipopolysaccharide (LPS) after pretreatment with placebo or 20 mg/day enalapril for 5 days or with a single dose of 20 mg of enalapril 2 h before LPS infusion. LPS infusion increased TNF levels 300-fold above normal, circulating (c) E-selectin levels by 425% (CI, 359%-492%), and P-selectin, VCAM-1, ICAM-1, and von Willebrand factor levels by 47%-74%. LPS infusion also enhanced ICAM-1 and CD11b expression 2- to 3-fold on monocytes. However, no differences were seen between treatment groups (P > 0.05), despite 95% inhibition of ACE activity by enalapril. Inhibition of ACE activity by enalapril does not influence plasma indices of endothelial activation after endotoxin infusion in healthy individuals. Our results do not support the concept of a beneficial clinical effect of enalaprilat in septicemia.
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PMID:Enalapril does not alter adhesion molecule levels in human endotoxemia. 1274 88

An increased risk of thrombembolic events in congestive heart failure (CHF) has been attributed to a hypercoagulable state including vascular endothelial dysfunction and platelet activation. After experimental myocardial infarction, male Wistar rats were treated with placebo, the ACE inhibitor trandolapril, the selective aldosterone receptor antagonist eplerenone or the combination of both, for 10 weeks. Platelet-bound fibrinogen and surface-expressed P-selectin were not modulated in rats without CHF compared with sham-operated animals, but were significantly increased in CHF rats (LVEDP>15 mmHg). In CHF rats, ACE inhibition significantly reduced platelet P-selectin expression while bound fibrinogen was not modulated. Eplerenone reduced P-selectin expression to a comparable extent, while platelet-bound fibrinogen was normalised. Combination therapy with eplerenone and trandolapril completely abolished both the increased P-selectin expression as well as fibrinogen binding. Phosphorylation of platelet vasodilator-stimulated phosphoprotein (VASP) at both Ser(157) and Ser(239), which reflects the activity of platelet inhibitors including nitric oxide, was significantly reduced in platelets from placebo-treated CHF rats, and was completely normalised by combination treatment, but only marginally increased by either mono-therapy. The results show that platelet activation was evident only in CHF rats. Monotherapy with ACE inhibition or eplerenone partially reduced this increased platelet activation, which was completely rescued to basal levels by combination therapy. Increased nitric oxide bioavailability can only partially explain the reduced platelet activation by eplerenone and ACE inhibition.
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PMID:Inhibition of platelet activation in congestive heart failure by aldosterone receptor antagonism and ACE inhibition. 1278 15

The aims of the present study were to determine the effects and mechanisms of angiotensin II (Ang II) on leukocyte-endothelium interactions and the role of Ang II in a novel model of ischemia/reperfusion (I/R) in the mouse colon. Ang II dose-dependently increased leukocyte rolling and adhesion in colonic venules. Importantly, Ang II-induced leukocyte rolling was completely inhibited by immunoneutralization of P-selectin, and leukocyte adhesion was abolished in lymphocyte function antigen-1 (LFA-1)-deficient mice. The P-selectin-dependent rolling was found to be a precondition for the subsequent LFA-1-dependent leukocyte adhesion. Moreover, Ang II-induced leukocyte responses involved generation of reactive oxygen species and up-regulation of CXC chemokines. Notably, CXC chemokines, but not Ang II, stimulated leukocyte chemotaxis in vitro. I/R increased gene expression of angiotensin converting enzyme (ACE) in the colon and plasma concentrations of Ang II. Inhibition of ACE and the type 1 angiotensin (AT1) receptor significantly decreased the I/R-induced leukocyte adhesion. Taken together, these novel findings demonstrate that Ang II exerts potent pro-inflammatory effects in the colonic microcirculation and that inhibition of Ang II expression or function protects against I/R-induced leukocyte responses in the colon. Thus, it is suggested that Ang II is a major target to control pathological inflammation in the colon.
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PMID:Role of angiotensin II in ischemia/reperfusion-induced leukocyte-endothelium interactions in the colon. 1500 61


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