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

---

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

Impaired cardiac function is frequently accompanied by peripheral vascular dysfunction and a pro-inflammatory condition, which may be associated with elevated levels of angiotensin II. We hypothesized that the magnitude of flow mediated dilatation (FMD) of the brachial artery of post myocardial infarction patients will correlate with serum levels of tumor necrosis factor alpha (TNFalpha) and C-reactive protein (CRP), and that treatment with angiotensin converting enzyme inhibitors (ACEI) will increase FMD by reducing TNFalpha and CRP. Patients were treated with low dose (10 mg/day) quinapril (Q) or enalapril (E) and their effects on FMD and inflammatory markers were evaluated after 8 and 12 weeks. Before treatment, in both groups FMD showed a low value (Q: 2.95+0.42% and E: 3.3+/-0.33%), whereas TNF-alpha (Q: 31.65+/-8.23 pg/ml and E: 29.5+/-5.9 pg/ml) and CRP (Q: 7.28+/-2.96 mg/ml and E: 7.08+/-3.02 mg/ml) were elevated. In the Q group, but not in the E group FMD increased significantly, (to 5.96+1.10%), whereas TNF-alpha (19.0+/-12.21 pg/ml) and CRP (to 3.91+/-1.82 mg/L) significantly decreased after 8 and 12 weeks of Q treatment. Moreover, the magnitude of FMD showed a strong inverse correlation with serum levels of TNF-alpha and CRP after Q treatment. Thus, in post myocardial infarction patients endothelial dysfunction assessed by FMD correlates with elevated levels of plasma inflammatory markers, and low dose quinapril improves endothelial function, likely by reducing vascular inflammation.
...
PMID:Correlation of flow mediated dilation with inflammatory markers in patients with impaired cardiac function. Beneficial effects of inhibition of ACE. 1632 70

The state of lipid transport function of the blood, blood contents of stable nitrogen metabolites, and proinflammatory cytokines (TNF-a and IL-1b) during therapy with simvastatin were studied in 29 patients receiving combination antihypertensive therapy with angiotensin converting enzyme inhibitors (ACEI) and verapamil. Lipid lowering action of simvastatin was realized just in 1 month of treatment and remained sustained for half a year (average duration). 6 months after addition of simvastatin to antihypertensive therapy substantial (58.4%, p=0.044) rise of plasma content of stable nitrogen metabolites took place. At the same time therapy with metoprolol in a similar group of patients exerted no considerable effect on blood plasma concentration of nitrate and nitrite anions. Lowering of median values of TNF-alpha from 20.13 (12.67-52.80) to 11.34 (3.31-31.29) pg/ml (p<0.0038) was also noted at the background of combination antihypertensive therapy. This happened without distinct affair with degree of lipid lowering action of simvastatin. The results of the study document positive effect of half year treatment of patients with concomitant hypertension and diabetes with simvastatin (10-20 mg/day) in combination with ACEI and verapamil on metabolism of nitric oxide and plasma content of TNF-alpha which realizes independently from degree of hypolipidemic action of simvastatin.
...
PMID:[Effect of 6-month therapy with simvastatin on lipid transport function of the blood and the state of endothelium in patients with diabetes and hypertension]. 1647 6

Skeletal muscle is a highly adaptable tissue. It responds to environmental and physiological challenges by changes in size, fibre type and metabolism. All of these responses are underpinned by our genes and it is therefore generally assumed that genetic variation between individuals may account for the differences in musculature and athletic capabilities between people. Research into the genetic influences of our muscle is at an embryonic stage, but some early insight into potential regulators has recently emerged, which is reflected in this review. Broad heritability, which appears to affect muscle size and strength more than metabolism has been assessed in twin and sibling studies. It appears to account for more inter-individual variation in the young as opposed to older people. However, the studies reported to date do demonstrate a large degree of diversity, which is probably predominantly due to different methodological approaches being adopted as well as distinct populations being studied. At a molecular level, there has been enormous progress in identifying regulators of atrophy and hypertrophy though the study of knock-out and transgenic animals and also through the utilisation of cell culture models. Among others, the insulin-like growth factors, calcineurin, desmin, myf5, mrf4, MyoD and myogenin have been identified as positive regulators of muscle size, while TNF-alpha, myostatin and components of the ubiquitin pathway have been recognized as regulators of muscle wasting. However, given the ethical and mechanistic constraints of performing similar studies in humans, difficulties have arisen when attempting to translate the animal and cell culture findings to humans. However, the current search for target "exercise genes" in humans has yielded the first successful results. Variations in the genes encoding for: the angiotensin converting enzyme, alpha-actinin 3, bradykinin, ciliary neurotrophic factor, interleukin-15, insulin-like growth factor II, myostatin and the vitamin D-receptor have all been found to account for some of the inter-subject variability in muscle strength or size. However, the influences of these genetic variations are somewhat weak, and not always reproducible and furthermore they are predominantly based in young healthy people. Hence, a key topic, namely the molecular mechanisms of muscle frailty in the elderly still remains to be elucidated.
...
PMID:Adaptive processes in skeletal muscle: molecular regulators and genetic influences. 1667 91

Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective.
...
PMID:Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period. 1671 19

We measured serum interleukin-2 receptor (sIL-2R), tumor necrosis factor-a (TNF-a), Fas receptor (sFas), nitric oxide (NO), and angiotensin converting enzyme (ACE) activity in 45 patients with congestive heart failure (CHF) of different etiologies. The relatioship between these bioindices and the severity of heart failure was analysed. Patients were classified according to the etiology of heart failure into: 15 patients with rheumatic valvular heart disease (RHD), 17 with ischemic heart disease (IHD) and 13 with idiopathic dilated cardiomyopathy (DCM). Patients were further classified according to severity of CHF following the New York Heart Association classification (NYHA) into: NYHA class II (n= 7), NYHA class III (n=20) and NYHA class IV (n=18). Eighteen healthy subjects were included as controls. Serum sIL-2R, TNF-alpha and sFas levels were determined by ELISA while serum NO and ACE levels were measured by colorimetric methods. Doppler Echocardiography was performed for all participants. Levels of sIL-2R, TNF-alpha, sFas, NO, and ACE were significantly higher in CHF patients than controls. Levels of the bioindices varied according to the CHF etiology. TNF-a level was the only one that had significant differences among different subgroups (RHD, IHD and DCM). The levels of sIL-2R, TNF-alpha, NO and sFas in patients with NYHA class IV were significantly higher than class II or III. Moreover, sIL-2R, TNF-alpha and NO levels were significantly higher in patients with diastolic dysfunction than patients with normal diastolic function. A significant positive correlations were found between sFas and both TNF-alpha and sIL-2R and between TNF-alpha and both NO and diastolic function. In addition, significant positive correlations were found between TNF-alpha and sIL-2R in both IHD and RHD patients and between sIL-2R and both ACE in IHD patients and diastolic function in DCM patients. It is concluded that a relationship exists between immune system activation, apoptosis and renin- angiotensin system in CHF and this may play a significant role in the pathophysiology and prognosis of the disease.
...
PMID:Proinflammatory cytokines, soluble Fas receptor, nitric oxide and angiotensin converting enzyme in congestive heart failure. 1673 38

A great number of association studies have been performed to identify the genes involved in the etiology and prognosis of sarcoidosis. We performed a systematic review of case-control studies through the PubMed database and evaluated them for a possible inclusion into a meta-analysis in order to assess whether the reported genetic polymorphisms are the risk factors of sarcoidosis. Case-control studies with clear diagnostic criteria and interventions were included. Only investigations of a single polymorphism/gene involvement in sarcoidosis reported more than five times were selected. Aggregating data from 12 studies on ID/ACE polymorphisms, the odds ratio (OR) for sarcoidosis, if the polymorphism was considered under the dominant genetic model, was not significantly increased: 1.19 (95% CI 0.98-1.43); OR under the recessive model was 1.20 (95% CI 0.98-1.46). In seven case-control studies on -308/TNF-alpha polymorphism, the OR for sarcoidosis if the polymorphism considered under the dominant genetic model was significantly increased at 1.47 (95% CI 1.03-2.08); the OR under the recessive model was 1.39 (95% CI 0.67-2.90). In conclusion, the results showed that the TNF-alpha genotype could be a significant risk factor for sarcoidosis, whereas the risk of sarcoidosis due to the ACE genotype was not substantially elevated.
...
PMID:Role of genetic polymorphisms in ACE and TNF-alpha gene in sarcoidosis: a meta-analysis. 1776 94

We first aimed to test the effect of anti-inflammatory drugs, etanercept and dexamethasone sodium phosphate (DSP), on the expression of inducible inflammatory signaling molecules (the bradykinin [BK] B(1) receptor [B(1)R], cyclooxygenase [COX]-2) in lipopolysaccharide (LPS)-treated rabbits. Preliminary experiments mostly based on a novel cellular model, rabbit dermis fibroblasts, showed that etanercept inhibited TNF-alpha-induced B(1)R expression ([(3)H]Lys-des-Arg(9)-BK binding), but that DSP also inhibited cytokine-induced B(1)R upregulation with less selectivity. LPS (100 microg/kg i.v.) induced the expression of the B(1)R (aortic contractility ex vivo, mRNA in hearts) and COX2 (immunoblots, heart extracts). However, the function of the BK B(2) receptor was unchanged (jugular vein contractility ex vivo). DSP pre-treatment profoundly reduced the induction of the B(1)R and COX2 whereas etanercept significantly inhibited only COX2 expression. The second aim was to verify whether chronic angiotensin converting enzyme (ACE) blockade in rabbits would induce B(1)R expression, as reported in other species. 14-Day enalapril oral dosing, but not treatment with the angiotensin receptor antagonist losartan, significantly increased aortic contractions mediated by B(1)Rs, however much less than LPS. Enalapril treatment did not increase COX2 expression but increased the ex vivo relaxation of the mesenteric artery mediated by endogenous prostaglandins. Chronic ACE inhibition recruits inflammatory signaling systems.
...
PMID:Cardiovascular expression of inflammatory signaling molecules, the kinin B1 receptor and COX2, in the rabbit: effects of LPS, anti-inflammatory and anti-hypertensive drugs. 1793 16

Tumour necrosis factor (TNF)-alpha, an important proinflammatory cytokine, has been implicated in the pathogenesis of sarcoidosis, a multi-systemic granulomatous disorder of unknown aetiology. Here, we report for the first time the association of TNF haplotypes and genotypes with sarcoidosis and its prognosis in the Indian population. Five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene were genotyped in a clinically well-defined cohort of North-Indian patients with sarcoidosis (n = 96) and their regional controls (n = 155). Serum TNF-alpha (sTNF-alpha) and serum angiotensin converting enzyme (SACE) levels were measured and correlated with genotypes and haplotypes. The TNFA_-1031 and TNFA_-863 polymorphisms were identified as markers for disease onset (FET P = 0.006 and 0.042 for TNFA_-1031 and TNFA_-863, respectively). Additionally, the allele A of LTA_NcoI polymorphism was shown to be prevalent in the 'no treatment' group (FET P = 0.005), while the G allele was associated with frequent relapses on drug withdrawal (P = 0.057). Furthermore, the TNFA-308G>A and the TNFA-238G>A polymorphisms were found to influence sTNF-alpha (P = 0.054 and 0.0005, respectively) and SACE levels (P = 0.0017 and 0.056, respectively). The haplotype frequencies were significantly different in the patients and the controls (P = 0.0067). The haplotype GTCCGG was identified as the major risk/susceptibility haplotype (P = 0.003) and was associated with increased SACE levels in the patient population. In conclusion, our study suggests an association of TNF polymorphisms with sarcoidosis.
...
PMID:Association of TNF polymorphisms with sarcoidosis, its prognosis and tumour necrosis factor (TNF)-alpha levels in Asian Indians. 1806 95

High blood pressure (HBP) is an important risk factor for cardiac, renal, and vascular dysfunction. Excess inflammation is the major pathogenic mechanism for HBP-induced target organ damage (TOD). N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a tetrapeptide specifically degraded by angiotensin converting enzyme (ACE), reduces inflammation, fibrosis, and TOD induced by HBP. Our hypothesis is that Ac-SDKP exerts its anti-inflammatory effects by inhibiting: 1) differentiation of bone marrow stem cells (BMSC) to macrophages, 2) activation and migration of macrophages, and 3) release of the proinflammatory cytokine TNF-alpha by activated macrophages. BMSC were freshly isolated and cultured in macrophage growth medium. Differentiation of murine BMSC to macrophages was analyzed by flow cytometry using F4/80 as a marker of macrophage maturation. Macrophage migration was measured in a modified Boyden chamber. TNF-alpha release by activated macrophages in culture was measured by ELISA. Myocardial macrophage activation in mice with ANG II-induced hypertension was studied by Western blotting of Mac-2 (galectin-3) protein. Interstitial collagen deposition was measured by picrosirius red staining. We found that Ac-SDKP (10 nM) reduced differentiation of cultured BMSC to mature macrophages by 24.5% [F4/80 positivity: 14.09 +/- 1.06 mean fluorescent intensity for vehicle and 10.63 +/- 0.35 for Ac-SDKP; P < 0.05]. Ac-SDKP also decreased galectin-3 and macrophage colony-stimulating factor-dependent macrophage migration. In addition, Ac-SDKP decreased secretion of TNF-alpha by macrophages stimulated with bacterial LPS. In mice with ANG II-induced hypertension, Ac-SDKP reduced expression of galectin-3, a protein produced by infiltrating macrophages in the myocardium, and interstitial collagen deposition. In conclusion, this study demonstrates that part of the anti-inflammatory effect of Ac-SDKP is due to its direct effect on BMSC and macrophage, inhibiting their differentiation, activation, and cytokine release. These effects explain some of the anti-inflammatory and antifibrotic properties of Ac-SDKP in hypertension.
...
PMID:Novel anti-inflammatory mechanisms of N-Acetyl-Ser-Asp-Lys-Pro in hypertension-induced target organ damage. 1817 15

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.
...
PMID:Role of inflammation in diabetic nephropathy. 1822 Jun 90


<< Previous 1 2 3 4 Next >>

---