Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the course of maintaining a cloned murine myocardium-derived endothelial cell line (mouse heart endothelial cell clone 5; MHEC5) a spontaneously transformed variant has been identified (clone MHEC5-T). On injection into histocompatible mice, clone MHEC5-T uniformly generated epithelioid haemangioendotheliomas. Clone MHEC5-T underwent significant additional alterations in addition to the acquisition of tumour-forming potential in vivo along with the diagnostic correlate of loss of cellular contact inhibition in vitro. Whereas the transformed cells maintained lectin-binding properties characteristic of endothelial cells, they lost the cell surface receptor(s) for acetylated low density lipoprotein and no longer bound antibodies to either angiotensin converting enzyme or von Willebrand factor-associated antigen. Vascular cell adhesion molecule-1 (VCAM-1), expressed constitutively on the parent clone, was down-regulated in the transformed cell line. The transformed cells acquired immunoreactivity to antibodies directed against cytokeratin, and they showed a markedly increased response to migration-inducing factors in vitro. The cell line described in this report demonstrates that the in vitro transformation of myocardium-derived endothelial cells can lead through transitional stages of differentiation to a new stable phenotype characterized by endothelial--to--epithelioid transition. The study of MHEC5-T cells, in addition to providing insight into the biology of cardiac neoplasms, may help to elucidate regulatory mechanisms involved in endothelial cell activation, transition and transformation.
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PMID:A transformed murine myocardial vascular endothelial cell clone: characterization of cells in vitro and of tumours derived from clone in situ. 765 44

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

Hypertension and coronary artery disease are intimately connected. The migration of circulating monocytes into the subendothelial occurs through the expression of some adhesion molecules on endothelial cells. The nuclear factor (NF)-kappaB, a redox-sensitive element, plays a key role in adhesion molecule gene induction. In this study we have compared the effects of two different angiotensin converting enzyme (ACE) inhibitors, one possessing an active sulfhydryl group (zofenopril) and one lacking this group (enalapril) on the cellular redox state (monitored by measuring intracellular reactive oxygen species and thiol status), expression of adhesion molecules, and activation of NF-kappaB in human umbilical vein endothelial cells (HUVECs). Zofenoprilat, the active form of zofenopril, significantly and dose dependently reduced the intracellular reactive oxygen species (ROS) and superoxide formation induced by oxidized low-density lipoprotein (ox-LDL) (P <.001) and tumor necrosis factor-alpha (TNF-alpha) (P <.001). Enalaprilat, the active form of enalapril, was ineffective. Zofenoprilat but not enalaprilat also decreased the consumption of the intracellular GSH induced by ox-LDL (P <.01) and TNF-alpha (P <.01). Although zofenoprilat significantly and dose dependently reduced the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and E-selectin induced by ox-LDL (P <.01) and TNF-alpha (P <.01) on HUVECs, enalaprilat did not. Ox-LDL and TNF-alpha increased the activation of NF-kappaB and the preincubation of HUVECs with zofenoprilat, but not with enalaprilat, dose dependently reduced its activation (P <.001). The conclusion is that the sulfhydryl (SH)-containing ACE inhibitors may be useful in inhibiting foam cell formation and thus slow the development of atherosclerosis.
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PMID:Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species. 1237 76

Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD). Although the pathogenesis of DN is multifactorial, local inflammatory stress may result from both the metabolic and hemodynamic derangements observed in DN. Inflammatory markers such as Interleukin-18 and Tumor Necrosis Factor (TNF)-alpha are increased in the serum of patients with diabetes and DN. This occurs at a very early stage of disease, and correlates with the degree of albuminuria. Recent data suggest that standard pharmacologic interventions for DN, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists, may have anti-inflammatory properties that are independent of their hemodynamic effect. Although inflammation is traditionally thought of as a process resulting in macrophage infiltration, current scientific progress has lead to the novel idea that even cells distant from the blood stream, such as podocytes, can produce cytokines and can express molecules that are part of the co-stimulatory pathway. A strong translational research effort is currently aimed at defining the role of such molecules in cells other than lymphocytes and macrophages. Experimental animal models have recently provided evidence that some acute phase markers of inflammation such as intracellular cell adhesion molecule-1 (ICAM-1), TNF-alpha and Monocytes Chemoattractant Protein-1 (MCP-1) may have a causative role in the development of DN. Here, we review the current evidence supporting the role of inflammation in the early phases of clinical and experimental DN. A complete understanding of inflammatory pathways activated in DN may lead to the discovery of earlier and more reliable markers of DN than albuminuria and the identification of novel therapeutic targets.
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PMID:Role of inflammation in diabetic nephropathy. 1822 Jun 90

Paraquat (1,1'-dimethyl-4,4'-bipyridinium) (PQ), is a nonselective contact herbicide that is highly toxic to humans. The kidney is affected during PQ intoxication. Dexamethasone (Dexa) has anti-inflammatory effects and is used to treat cases of PQ poisoning. We investigated in rat kidney hemodynamic effects and immunohistochemical characteristics of Dexa treatment in acute PQ poisoning. Adult male rats were divided into four groups: 1, untreated control; 2, treated with 100 mg/kg Dexa; 3, treated with 25 mg/kg PQ; 4, treated with PQ + Dexa. Mean arterial pressure (MAP) and heart rate (HR) were recorded during the experimental period (2 h). Tissues were removed after 2 h and immunohistochemistry was performed after 24 h. Paraffin sections of kidney were prepared and anti-cyclo-oxygenase-1 (COX-1), anti-cyclo-oxygenase-2 (COX-2), anti-angiotensin converting enzyme (ACE), anti-aquaporin-1 (AQU-1), anti-vascular cell adhesion molecule (VCAM) primary antibodies were used for immunohistochemical examination. Immunoreactivities were scored as: (1) minimal, (2) weak, (3) mild, (4) moderate, (5) strong and (6) very strong. MAP and HR were measured at 10 min, 20 min, 1 h and 2 h. MAP at 10 and 20 min and 1 h was increased in the Dexa group. HR also was increased in all groups compared to controls at 2 h. Compared to groups 2 and 4, MAP values decreased significantly in group 3 at 1 h. The intensity of all of immunoreactivities was decreased in group 2. In group 3, immunoreactivities of COX-1, COX-2 and ACE were decreased compared to the control and the other groups, whereas AQU-1 and VCAM immunoreactivities were the same as the control group. ACE and VCAM immunoreactivities were decreased in group 4 compared to the control group, while COX-1, COX-2 and AQU-1 immunoreactivities were close to those of the control group. Dexa appears to be useful for treating PQ intoxication.
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PMID:Effects of high doses of dexamethasone on hemodynamic and immunohistochemical characteristics of acute paraquat intoxication in rat kidneys. 2679 20