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)

A majority of angiogenic factors has been shown to be produced by macrophages. This review will give a concise description of their biochemical nature, their isolation from macrophages and their angiogenic activity. Among the factors with mitogenic effects on endothelial cells are basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha) and very probably insulin-like growth factor-1 (IGF-1). Other secretory products such as angiotropin and human angiogenic factor (HAF) are nonmitogenic but promote angiogenesis by inducing migration of endothelial cells. Prostaglandins, platelet-derived growth factor (PDGF), granulocyte-macrophage- and granulocyte-colony stimulating factor (GM-CSF, G-CSF), interleukin 6 (IL-6) and angiotensin converting enzyme (ACE) have also been shown to be angiogenic, but their mode of action is still to be clearly defined. As the extracellular matrix appears to be involved in the control of angiogenesis, macrophage-derived factors that can alter this structure via degradation or via the clotting system will also be discussed. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1) and transforming growth factor-beta (TGF-beta) have complex actions on endothelial cells, and can partially inhibit angiogenesis. Among the factors which solely inhibit neovascularization are the interferons. As it is not known whether all of these factors play a role in angiogenesis in vivo attempts to detect them in situ during the course of neovascularization will be described. Finally macrophages will be discussed as cells that may not be mandatory for each phase of the angiogenic process but whose angiogenic capabilities are comprehensive and unsurpassed by any other cell.
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PMID:Macrophage-derived angiogenesis factors. 178 30

Experimental diabetes is associated with renal enlargement and glomerular hyperfiltration. Possible mechanisms for these changes could be the direct effects of growth factors such as insulin-like growth factor-1 and angiotensin II. We investigated whether treatment with trandolapril, an angiotensin converting enzyme inhibitor, prevented renal enlargement in streptozotocin-diabetic rats. Seven groups of male Wistar rats were studied: C (control + placebo); CL (control + low-dose trandolapril, 0.01 mg.kg-1.day-1); CH (control + high-dose trandolapril, 0.5 mg.kg-1.day-1; DP (diabetic + placebo); DI (diabetic, insulin-treated); DL (diabetic + low-dose trandolapril); DH (diabetic + high-dose trandolapril) and DI (diabetic + insulin). From day 2 glucose concentrations and body weight were similar in the non-diabetic and diabetic animals treated with insulin. Diabetic animals treated with placebo and low-dose trandolapril weighed significantly less compared to the control group. The diabetic groups, not treated with insulin, showed marked hyperglycaemia throughout the study. Kidney weight was greater in the diabetic, non insulin-treated groups compared with the control and insulin-treated groups. After 24 h of diabetes, kidney insulin-like growth factor-1 content was significantly increased from baseline levels in groups DP, DL and DH but by 48 h these levels had returned to normal. Renal tissue angiotensin converting enzyme activity was similar in groups C and DI but significantly reduced in all trandolapril-treated animals. Despite inhibiting renal angiotensin converting enzyme activity renal enlargement with increased tissue insulin-like growth factor-1 still occurred. This suggests that neither angiotensin II nor glomerular hyperfiltration, with raised intraglomerular pressure, play a role in the initial renal enlargement seen in experimental diabetes. Renal accumulation of insulin-like growth factor-1 appears to be an important factor in early renal hypertrophy and its effects are not modulated by angiotensin converting enzyme or angiotensin II.
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PMID:Renal enlargement and insulin-like growth factor-1 accumulation in the Wistar rat model of experimental diabetes is not prevented by angiotensin converting enzyme inhibition. 863 68

Glucose homeostasis is maintained by a balance between the release and action of insulin, and the counterregulatory responses mediated principally by glucagon, catecholamines, growth hormone and cortisol. Hence, the effects of a drug on glucose metabolism may be mediated by any of these agents singly or in combination. Host factors, such as inherent glucoregulatory mechanisms, concurrent diseases, organ function and concomitant medications also increase the risk of drug-induced disturbances of glucose homeostasis in susceptible individuals. By far the most important agents causing hypoglycaemia are insulin and the sulphonylureas. Alcohol (ethanol), over-zealous glycaemic control, hypoglycaemic unawareness, detective counterregulation especially in insulin-dependent diabetes mellitus (IDDM), and renal and liver impairment are all important predisposing factors. Although antihyperglycaemic agents such as metformin and alpha-glucosidase inhibitors do not cause hypoglycaemia alone, they may enhance the hypoglycaemic effects of potent hypoglycaemic agents such as insulin and sulphonylureas. On the other hand, the potential hypoglycaemic effects of ACE inhibitors, alpha-blockers, lipid-lowering agents and recombinant human insulin-like growth factor demonstrated in experimental settings, are of potential therapeutic interest. Iatrogenic hypoglycaemia and intensive insulin treatment are associated with hypoglycaemic unawareness which may be obviated by meticulous avoidance of hypoglycaemia. Effective patient education remains an important preventive measure. Oral glucose is used to treat mild hypoglycaemic episodes while more severe episodes are treated by intravenous glucose or glucagon. Nasal glucagon and theophylline are other experimental measures to improve recovery from hypoglycaemia. In refractory hypoglycaemia due to hyperinsulinaemia such as during sulphonylurea overdosage or quinine treatment, the long-acting somatostatin, octreotide, may suppress insulin release and restore euglycaemia. Diuretics, beta-blockers, sympathomimetics, corticosteroids and sex hormones are commonly prescribed drugs which may have adverse effects on carbohydrate metabolism especially in patients with diabetes mellitus or those who are at risk of developing glucose intolerance. Pentamidine was frequently associated with dysglycaemia due to its pancreatic beta-cell cytotoxic effects but is now used less often to treat Pneumocystis carinii pneumonia in immunosuppressed patients. Despite the large number of anecdotal reports of drug-induced disturbances of glucose metabolism, many of the so-called adverse drug reactions were either idiosyncratic or coincidental. Nevertheless, they emphasise the complex nature of glucose homeostasis and its potential interactions with drugs, host factors and disease states. An understanding of these relationships may allow more critical interpretation of these clinical observations, better prediction of drug induced adverse effects on carbohydrate metabolism and the implementation of more rational therapy. Hence, the hypoglycaemic effects of a drug may be turned to a therapeutic advantage in patients with glucose intolerance. Similarly, the hyperglycaemic effect of a drug may help to treat refractory hypoglycaemia.
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PMID:Drug-induced disorders of glucose metabolism. Mechanisms and management. 888 64

Congestive heart failure is a multiple aetiology, high prevalence, poor prognosis cardiovascular disorder. Medical treatment of dilated cardiomyopathy is aimed at alleviating the symptoms of heart failure. Diuretics, ACE inhibitors and very recently, beta-blockers have been shown to have favourable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The roles of GH and IGF-1 as modulators of myocardial structure and function are well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, whereas IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases and, in addition, an impaired cardiac efficiency is observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by haemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is caused by ventricular dilatation with abnormal wall thickening, which leads to impaired cardiac performance; therefore, based on the evidence available for GH we would expect beneficial effects from the use of GH in these patients. Several papers highlight the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small nonblind studies, both short and long term GH treatment have demonstrated beneficial effects in patients with heart failure secondary to ischaemic or idiophatic cardiomyopathy. Recently, two randomised, placebo-controlled studies, did not show significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance, might be an important feature of severe heart failure and explain the different responses to GH therapy seen in different patients. Whether GH treatment will finally find a place, and with which modalities, in the treatment of heart failure remains to be established.
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PMID:Role of growth hormone in chronic heart failure. Therapeutic implications. 1108 97

The molecular mechanisms regulating uterine relaxation and contraction during pregnancy are poorly understood. In the present study, we used for the first time a functional genomics approach applying gene array technology to identify novel candidate genes involved in the regulation of uterine quiescence and contractility during pregnancy. The purpose of this approach was to obtain a molecular snapshot of the expression profile of gene transcripts as a function of the time dependent process regulating myometrial quiescence. Using this approach, we found several genes whose expression in human myometrium was altered with the onset of labour. For example, the expression of insulin-like growth factor (IGF)-II, calgranulin A and B, and G-protein coupled receptor were decreased while the expression of IGF-binding proteins, Ca(2+)/CaM binding protein kinase C substrate, and angiotensin converting enzyme were increased in the labouring, compared with non-labouring, pregnant myometrium. The differentially-expressed genes include several genes whose roles in myometrial quiescence are yet to be understood, although they have been reported to regulate vascular smooth muscle tone. Our findings illustrate the advantage of a functional genomics approach over a single gene analysis in identifying a large number of novel and potentially important genes mediating uterine smooth muscle contractile activity.
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PMID:Application of a functional genomics approach to identify differentially expressed genes in human myometrium during pregnancy and labour. 1110 97

Molecular biologic research on erectile dysfunction (ED), especially the elucidation of NO-cGMP signaling pathway which plays an important role on modulating corpus cavernosum smooth muscle dilation, has been made the great advance in past ten years. The further research on the penile erection related genes including nitric oxide synthase (NOS), phosphodiesterases (PDEs), K+ channal, insulin-like growth factor (IGF), heme oxygenase (HO), vascular endothelial growth factor (VEGF), cyclic GMP-dependent kinase (cGK I), angiotensin converting enzyme (ACE) and growth factor (GF) etc, has given the theoretical evidence for the clinical treatment of ED in future.
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PMID:[Advances in the research about penile erection related genes]. 1247 29

Angiotensin II (Ang II) has been implicated in muscle protein loss in cachexia. To determine whether the Ang I/II system directly inhibits protein synthesis in muscle their effect has been monitored in vitro using murine myotubes as a surrogate model system. Ang I inhibited protein synthesis by 40-50% over the concentration range of 0.05-2.5 microM within 30 min of addition, and the inhibition remained relatively constant over 24 h. The effect was attenuated by co-incubation with the angiotensin converting enzyme inhibitor imidaprilat (50 microM) suggesting that inhibition of protein synthesis was due to the formation of Ang II. Ang II also inhibited protein synthesis by 40-50% over the concentration range of 0.1-5 microM, and the inhibition also remained relatively constant between 30 min and 24 h after addition. The effect was attenuated by insulin-like growth factor-1 (IGF-1) (25-100 ng/ml). Thus, Ang I/II have the ability to induce muscle atrophy through inhibition of protein synthesis.
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PMID:Angiotensin II directly inhibits protein synthesis in murine myotubes. 1639 30

Diabetic nephropathy (DN) can be delayed by the use of angiotensin-converting enzyme inhibitors (ACEi). The mechanisms of ACEi renal protection are not univocal. To investigate the impact of bradykinin B(2) receptor (B2R) activation during ACE inhibition, type II diabetic mice (C57BLKS db/db) received for 20 wk: 1) ACEi (ramipril) alone, 2) ACEi + HOE-140 (a specific B2R antagonist), 3) HOE-140 alone, or 4) no treatment. The development of DN, defined by an increase in albuminuria and glomerulosclerosis, was largely prevented by ACEi treatment (albuminuria: 980 +/- 130 vs. 2,160 +/- 330 mg/g creatinine; mesangial area: 22.5 +/- 0.5 vs. 27.6 +/- 0.3%). The protective effect of ramipril was markedly attenuated by B2R blockade (albuminuria: 2,790 +/- 680 mg/g creatinine; mesangial area: 30.4 +/- 1.1%), whereas HOE-140 alone significantly increased albuminuria. Despite such benefits, glomerular filtration rate remained unchanged, probably because of the combination of the hypotensive effect of diabetes in this model and the renal hemodynamic action of ramipril. Finally, the renal protective effect of ACEi was associated with a marked decrease in glomerular overexpression of insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta pathways, but also in advanced glycation end product receptors and lipid peroxidation assessed by 4-hydroxy-2-nonenal (4-HNE) adducts. Concomitant blockade of B2R partly restored glomerular overexpression of IGF-1 receptor beta and 4-HNE complexes. These results support the critical role of B2R activation in the mediation of ACEi renal protection against DN and provide the rationale to examine the benefit of B2R activation by itself as a new therapeutic approach for DN.
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PMID:Pharmacological blockade of B2-kinin receptor reduces renal protective effect of angiotensin-converting enzyme inhibition in db/db mice model. 1836 57

Aging is associated with progressive decline of skeletal muscle mass and function. This condition, termed sarcopenia, is associated with several adverse outcomes, including loss of autonomy and mortality. Due to the high prevalence of sarcopenia, a deeper understanding of its pathophysiology and possible remedies represents a high public health priority. Evidence suggests the existence of a relationship between declining growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels and age-related changes in body composition and physical function. Therefore, the age-dependent decline of GH and IGF-1 serum levels may promote frailty by contributing to the loss of muscle mass and strength. Preclinical studies showed that infusion of angiotensin II produced a marked reduction in body weight, accompanied by decreased serum and muscle levels of IGF-1. Conversely, overexpression of muscle-specific isoform of IGF-1 mitigates angiotensin II-induced muscle loss. Moreover, IGF-1 serum levels have been shown to increase following angiotensin converting enzyme inhibitors (ACEIs) treatment. Here we will review the most recent evidence regarding age-related changes of the GH/IGF-1 axis and its modulation by several interventions, including ACEIs which might represent a potential novel strategy to delay the onset and impede the progression of sarcopenia.
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PMID:Modulation of GH/IGF-1 axis: potential strategies to counteract sarcopenia in older adults. 1876 7

The objective of this study was to determine the ontogenetic profiles in left and right ventricle of genes implicated in cardiac growth, including mineralocorticoid (MR) and glucocorticoid (GR) receptor, 11 beta-hydroxysteroid dehydrogenase (11beta-HSD) 1 and 2 and genes of the angiotensin system and insulin-like growth factor (IGF) family. Samples from left and right ventricles (LV, RV) were collected from hearts of sheep fetuses at 80, 100, 120, 130, and 145 days of gestation and from newborn lambs. Quantitative real-time PCR was performed to determine the MR, GR, 11beta-HSD 1 and 2, angiotensin converting enzyme (ACE) 1 and 2, IGF1, IGF2, IGF receptors IGF-1R and IGF-2R, and IGF-binding proteins (IGFBP) 2 and 3. In the LV, MR and GR both decreased toward term. In the RV, MR and GR expression did not decrease, but both 11beta-HSD 1 and 2 mRNA levels increased after birth. ACE1 expression in LV and RV sharply increases just before parturition, whereas ACE2 decreased in the LV and RV in late gestation. IGF2, IGF2R, and IGFBP2 expression levels substantially decreased in late gestation in LV and RV; IGF2R also decreased with age in LV. These patterns suggest that reduced expression of genes related to IGF and angiotensin II action occur as proliferative activity declines and terminal differentiation occurs in the late gestation fetal heart.
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PMID:The ontogeny of genes related to ovine fetal cardiac growth. 1883 62


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