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)

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery. 788 59

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

At present the induction and elicitation of an ACD with potent contact allergens such as DCP appear to be the most effective, but still not definitively curative, approach in treating extensive forms of AA. Experimental data suggest that cytokines and growth factors such as IL 1 beta are involved in the pathogenesis of AA as well as the therapeutic effect mediated by contact sensitizers. It seems reasonable to assume that factors inherent in the late phase of ACD modulate a T-cell mediated mechanism responsible for AA, thus inducing hair regrowth. Such counteracting activities are most likely mediated by proinflammatory cytokines such as TNF-alpha, IL-10, or TGF-beta 1. This hypothesis may oversimplify the underlying immunologic mechanisms, but the effectiveness of topical immunotherapy in AA would be compatible with this concept. This mode of treatment is, however, a rather rough approach and recurrences are possible. It is hoped that advances in basic science will eventually allow us to find a more specific mode of treatment.
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PMID:Topical immunotherapy in alopecia areata. What, how, and why? 923 32

Heart failure is a common and increasing public problem. Neurohormonal activation plays a role in the pathophysiology of heart failure, but is probably also affected by cytokines. We studied 75 patients with heart failure NYHA functional class II and III-IV, who were treated with angiotensin converting enzyme inhibitor (enarenal), diuretics (furosemide) and digoxine. Their mean age was 63.9 years/range 65-86/, left ventricular ejection fraction in the patients NYHA functional class II and III-IV classes was 68.9% and 47.3% respectively; 12 were females. Significant improvements in NYHA classification were shown. The levels plasma TNF-alpha (tumor necrosis factor-alpha) and interleukin-6 (IL-6) were analysed before and after therapy. The authors showed increased plasma levels TNF-alpha and IL-6 in patients with chronic heart failure. After the treatment the plasma IL-6 levels decreased only in the patients III-IV NYHA functional classes, whereas the treatment had no effect on the plasma TNF-alpha levels.
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PMID:[Do cytokines have any value in the patients with chronic blood circulation insufficiency?]. 1052 13

Recent work from this laboratory demonstrated that apoptosis of pulmonary alveolar epithelial cells (AEC) in response to Fas requires angiotensin II (ANGII) generation de novo and binding to its receptor (Wang et al., 1999b, Am J Physiol Lung Cell Mol Physiol 277:L1245-L1250). These findings led us to hypothesize that a similar mechanism might be involved in the induction of AEC apoptosis by TNF-alpha. Apoptosis was detected by assessment of nuclear and chromatin morphology, increased activity of caspase 3, binding of annexin V, and by net cell loss inhibitable by the caspase inhibitor ZVAD-fmk. Purified human TNF-alpha induced dose-dependent apoptosis in primary type II pneumocytes isolated from rats or in the AEC-derived human lung carcinoma cell line A549. Apoptosis in response to TNF-alpha was inhibited in a dose-dependent manner by the nonselective ANGII receptor antagonist saralasin or by the nonthiol ACE inhibitor lisinopril; the inhibition of TNF-induced apoptosis was maximal at 50 microgram/ml saralasin (101% inhibition) and at 0.5 microgram/ml lisinopril (86% inhibition). In both cell culture models, purified TNF-alpha caused a significant increase in the mRNA for angiotensinogen (ANGEN), which was not expressed in unactivated cells. Transfection of primary cultures of rat AEC with antisense oligonucleotides against ANGEN mRNA inhibited the subsequent induction of TNF-stimulated apoptosis by 72% (P < 0.01). Exposure to TNF-alpha increased the concentration of ANGII in the serum-free extracellular medium by fivefold in A549 cell cultures and by 40-fold in primary AEC preparations; further, exposure to TNF-alpha for 40 h caused a net cell loss of 70%, which was completely abrogated by either the caspase inhibitor ZVAD-fmk, lisinopril, or saralasin. Apoptosis in response to TNF-alpha was also completely inhibited by neutralizing antibodies specific for ANGII (P < 0.01), but isotype-matched nonimmune immunoglobulins had no significant effect. These data indicate that the induction of AEC apoptosis by TNF-alpha requires a functional renin/angiotensin system (RAS) in the target cell. They also suggest that therapeutic control of AEC apoptosis in response to TNF-alpha is feasible through pharmacologic manipulation of the local RAS.
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PMID:Apoptosis of lung epithelial cells in response to TNF-alpha requires angiotensin II generation de novo. 1102 47

The important neuroendocrine systems implicated in heart failure are reviewed here, with special emphasis on their possible role in pathophysiology and the chances of pharmacological intervention. The part played by the sympathetic nervous system and the renin-angiotensin-aldosterone system and the beneficial effects of beta-blockers, ACE inhibitors, and angiotensin II antagonists are well-established. The involvement of vasopressin, endothelin-1, ANP, BNP, and TNF-alpha and the interventional possibilities relating to these hormones are also discussed. It is concluded that, in addition to the known interventional principles of neuroendocrine activation, there is a series of new exciting principles and some of them might become important in the future.
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PMID:[Neuroendocrine activation in heart failure I. Pathophysiology and pharmacological intervention]. 1109 49

Insulin resistance and hyperinsulinemia have been observed in over 70% of the nonobese, nondiabetic subjects with essential hypertension (HT). Alpha-1 blockers, ACE-antagonists, long-acting Ca blockers including nifedipine CR, some form of beta-blockers, tilisolor, which is reported to increase blood flow, improve insulin sensitivity when blood pressure is better controlled. Decrease of serum potassium during insulin sensitivity test and intraplatelet free Ca2+ concentration is positively and negatively correlated with insulin sensitivity, respectively. Blood pressure is correlated with insulin resistance, which is also observed in secondary HT. The resistance is correlated with salt sensitivity as well as impaired nocturnal fall of blood pressure. These suggest the possible association of insulin resistance with altered intracellular cation metabolism. Insulin resistance and associated hyperinsulinemia have been observed in effort as well as vasospastic angina pectoris (VSAP), atherothrombotic cerebral infarction, and in ASO without obesity, HT, or diabetes, suggesting the resistance resulting from endothelial dysfunction. Insulin resistance has been observed in heart failure and is correlated with angiotensin II. Resistance is also observed in hypertrophic cardiomyopathy and is partially correlated with TNF-alpha. These results indicate that insulin resistance seem to be multifactorial. An effort to normalize insulin sensitivity is crucial to eliminate multiple risk factors as well as to prevent the progression of atherosclerotic vascular lesions.
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PMID:Multifactorial insulin resistance and clinical impact in hypertension and cardiovascular diseases. 1187 61

Pulmonary fibrosis can be observed as an end state in a number of chronic inflammatory pulmonary diseases. Although the mechanisms by which lung fibrosis develops are not fully ascertained, recent findings suggest that oxidative stress may play an important role in the pathogenesis of tissue fibrosis affecting apoptosis of both structural and inflammatory cells and altering the cytokine microenvironment balance. Damage and alteration of alveolar epithelial cells is one of the hallmarks of interstitial lung fibrosis. Recently, it has been demonstrated that the presence of oxidative stress may lead to the damage, activation and/or apoptosis of alveolar epithelial cells either directly, through an imbalanced intracellular redox equilibrium, or indirectly, by activating redox-sensitive effector pathways, such as transcription factors and angiotensin converting enzyme, increasing the conversion of angiotensinogen into angiotensin II that can be considered a mediator of oxidative stress, capable of inducing apoptosis. Furthermore, it has been demonstrated that angiotensin II acts as a proinflammatory cytokine and is effective in activating fibroblasts through the release of transforming growth factor (TGF-beta). As well as activation, differentiation, proliferation and apoptosis of fibroblasts seem related to the oxidant/antioxidant balance, and the maintenance of a high intracellular level of reduced glutathione (GSH) is considered crucial in providing a reducing environment within the cell, able to protect against oxidative stress. In those conditions where oxidants, either inhaled or produced by inflammatory cell, increase, the ratio between GSH and oxidized glutathione (GSSH) may lower, influencing a variety of cellular redox-sensitive signaling processes such as the activation of nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) that lead to a transcriptional up-regulation of a number of genes involved in inflammation and/or fibrogenesis, including cytokines [interleukin (IL)-1,, tumor necrosis factor (TNF-alpha), IL-6] chemokines (IL-8), adhesion molecules (VCAM-1, ICAM-1) and growth factors (GM-CSF). In addition, several studies have shown that oxidative stress may also affect the immune response by inducing an up-regulation of HLA-DR as well as the expression of two costimulatory molecules such as CD40 and CD86, determining a persistent state of immune activation, and affecting the Th1/Th2 balance, modulating the T-cell effector response towards the Th2 phenotype. It is clear that a better understanding of the precise sequence of events that make the difference between normal tissue repair and fibrosis, including the role played by oxidative stress, will certainly improve our therapeutic approach to pulmonary fibrosis.
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PMID:Role of oxidative stress in pulmonary fibrosis. 1261 77

The pulmonary granulomatous diseases may be staged using clinical examination, pulmonary function tests, ⁶⁷Ga scans, chest X-rays, BAL and serum ACE levels; furthermore, these disorders are clearly associated to changes in lymphocyte subpopulations, CD4+/CD8+ ratio and surface receptors; in particular, T cell activation characterizes early alveolitis phase, while activated macrophages and related cytokines prevail in granulomata and fibrosis development. In this study, we dosed the serum and blood concentrations of IL-6 (a well-known pro-inflammatory cytokine), sIL-2R (marker of T-cell activation), TNF-alpha and IFN-gamma (associated with the granuloma development), in patients affected by active or inactive sarcoidosis, primary tuberculosis, idiopathic pulmonary fibrosis and healthy control subjects, using the ELISA method. Cytokines assay showed significant changes only in subjects with primary tuberculosis and active sarcoidosis; infact, primary tuberculosis was characterized by high values of IL-6 and IFN-gamma both in peripheral blood and in BAL, with high values of sIL-2R in BAL; patients with active sarcoidosis showed high levels of IFN-gamma and TNF-alpha both in BAL and in peripheral blood, associated to an increase of serum sIL-2R levels. Our data confirm that the compared assay of these cytokines in peripheral blood and BAL specimens, may be useful to diagnose and to assess the disease activity in pulmonary granulomatous diseases; in particular, the levels of sIL-2R are a marker of the alveolitis phase, while TNF-alpha and IL-6 levels discriminate patients with sarcoidosis or tuberculosis granulomata, respectively.
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PMID:Cytokines assay in peripheral blood and bronchoalveolar lavage in the diagnosis and staging of pulmonary granulomatous diseases. 1265 92

The efficiency of the developed scheme for a drug prophylaxis of chronic cardiac insufficiency (CCI) in patients with diabetes mellitus I (DM I) of autoimmune genesis (subtype B) was evaluated; such scheme comprised the inhibitors of angiotensin converting enzyme (ACE) of different chemical structures and a biological response modifier (BRM)--glutoxime, which were prescribed with regard for a changed biological rhythm of hemodynamic as well as of metabolic and immune profiles of patients. The following parameters were examined: cardiohaemodynamics, the content of cortisol, insulin, ACTH, TTH and thyroxin in blood, of transport proteins and of the concentration of IL-1 and TNF-alpha in blood. It was established that the use of ramipril and fosinopril combined with the glutoxime BRM within the scheme of drug prophylaxis of CCI concomitant with DM I was accompanied by an effective removal of desynchronosis of the immune-endocrine system in the discussed category of patients.
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PMID:[Chronopharmacological approaches to the therapeutic prophylaxis of chronic cardiac insufficiency in type I diabetes mellitus]. 1274 55


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