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)

1. The effects of purified diets containing 70% glucose or 70% fructose on the activation state of hepatic pyruvate dehydrogenase (PDHa), activity of mitochondrial PDH kinase, plasma triacylglycerols (TG) and hepatic lipogenesis de novo in rats were measured. 2. Plasma TG were significantly increased in the fructose-fed compared with the glucose-fed group (125 +/- 45 mg/dl versus 57 +/- 19 mg/dl; P less than 0.002) after 3-5 weeks on the diet despite less daily food intake. 3. Hepatic PDHa in fructose-fed rats was 144% of the value in glucose-fed rats (15.4 +/- 1.2% versus 10.7 +/- 0.5%; P less than 0.002), whereas cardiac muscle PDHa was not different (45.5 +/- 6.6% versus 41.0 +/- 7.8%). 4. Intrinsic hepatic PDH kinase activity was decreased to 34% of glucose-fed values by fructose feeding (-k = 3.56 +/- 0.39 versus 10.41 +/- 1.85 min-1; P less than 0.005). 5. The fractional contribution to very-low-density-lipoprotein palmitate from hepatic lipogenesis de novo, measured by a stable-isotope mass-spectrometric method, was 10.49 +/- 2.42% (n = 8) in fructose-fed rats versus 5.55 +/- 1.38% (n = 9) in glucose-fed rats (P less than 0.05), and 2.66 +/- 2.39% (n = 3) in chow-fed rats (P less than 0.05 versus fructose-fed group). The absolute contribution to circulating TG from lipogenesis de novo was also significantly higher in the fructose-fed than in the glucose-fed group (14.9 +/- 5.1 mg/dl versus 2.9 +/- 0.6 mg/dl; P less than 0.05) 6. Portal insulin concentrations were significantly higher in the fructose-fed rats (206 +/- 49 mu-units/ml versus 81 +/- 15 mu-units/ml; P less than 0.05). 7. In conclusion, dietary fructose appears to have a specific activating effect on hepatic PDH, mediated at least in part by inhibition of PDH kinase. These results are consistent with increased flux through hepatic PDH and synthesis of new fat, not just increased re-esterification of non-esterified fatty acids.
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PMID:Mechanisms of fructose-induced hypertriglyceridaemia in the rat. Activation of hepatic pyruvate dehydrogenase through inhibition of pyruvate dehydrogenase kinase. 155 57

Experimental myocardial infarction is a model of cardiac overload due to amputation of part of the cardiac muscle. The development of cardiac failure depends on the size of the infarct and the time factor. This model of overload is associated with changes of the phenotype of the remaining healthy muscle and with peripheral vascular modifications partially dependent of the activation of pressor and/or deactivation of dilator systems. These changes are proportional to the size of the infarction at a given time after induction of the model. The degree of right ventricular hypertrophy and the decrease in blood pressure reflect the severity of infarction and the deterioration of the remaining myocardial function, affecting the haemodynamics both before and after the left ventricle. The increases in the 1/3 forms of isomyosins, the amount of subendocardial collagen, the biosynthesis, stocking and secretion of ANF are related to the infarct size and degree of overload. Similarly, the concentration of cyclic GMP is proportional to the infarct size. These parameters reflect ventricular overload, the increase of stress and energy deprivation of the remaining healthy muscle. The activation of peripheral pressor systems is also dependent on the infarct size reflects the effect of cardiac pump dysfunction on the kidney, liver, brain and endothelium. Large infarcts are associated with increased circulating renin and renal concentrations, with a decrease in angiotensinogen levels related to its consumption by the renin and to reduced hepatic synthesis and also with increased secretion and biosynthesis of vasopressin by the hypothalamus. In this model, Perindopril is beneficial by decreasing the cardiac load. It reduces the blood pressure, causes regression of bi-auricular and right ventricular hypertrophy. Changes in myosin isoenzyme configuration regress and subendocardial fibrosis and ANF concentrations are normalised. The effects of ACE inhibitors in this context, though very beneficial, are limited by the impossibility of normalising cardiac load and stress when the initial amputation of cardiac contractile mass exceeds 40%.
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PMID:[Experimental myocardial infarction in the rat. Effect of perindopril]. 166 27

Eleven patients with congestive heart failure class II-IV (NYHA) caused by ischemic heart disease were studied before and three months after adding enalapril to their treatment with furosemide. After an infarction the heart dilates gradually, mainly as a result of slippage of myocardial fiber bundles. It is known that the addition of an ACE-inhibitor to the medical treatment unloads the heart and gradually, within a period of 3 months, reduces heart size. Objectives of this study were to demonstrate remodelling by recording diastolic pressure-volume relations before and after treatment. The study addresses the question of whether regression of dilation, induced by the ACE-inhibitor treatment, improves the oxygen supply-demand ratio and, as a result, the contractility of the heart muscle. Treatment resulted in a reduction of vascular resistance (1479 to 1182 dyn.s.cm-5, p less than 0.05) and of the left ventricular end-diastolic (130 to 108 ml per m2 body surface area, p less than 0.05) and end-systolic (102 to 81 ml per m2 body surface area, p less than 0.01) volume index. The slope of the end-systolic pressure-volume relation, measured using vena cava occlusion and beat-to-beat recording of pressure and volume loops, remained unchanged. Indices of oxygen-supply demand ratio such as a drop of ejection fraction during exercise and parameters of active diastolic relaxation also did not change. Addition of an ACE-inhibitor induces regression of ventricular dilation, but no indications were found that it improves the condition of the cardiac muscle.
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PMID:Cardiac remodelling and myocardial contractility in patients with congestive heart failure treated with furosemide and enalapril. 182 82

The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.
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PMID:Inotropic effects of angiotensin II on human cardiac muscle in vitro. 224 22

Recent evidence suggests that the most common form of idiopathic cardiomyopathy in our altitudes, the dilated cardiomyopathy (DCM), is a post-infectious autoimmune disease which is triggered by virus infections. In animal experiments, the development of the coxsackie virus B3 myocarditis to a congestive cardiac insufficiency resembling the clinical picture of DCM was demonstrated. In mice, species-dependent varying disease courses could be observed, which point to a genetically different behaviour of the animals' immunological reactions, either humoral or T-cell mediated immune reactions being responsible. In comparison with non-DCM patients, patients with DCM and chronic myocarditis exhibit significantly higher coxsackie virus antibody titres. Obviously, also a differently long viral persistency in the cardiac muscle plays a role, as enterovirus-specific RNA was detected in myocardial biopsies from patients with DCM. Along with myocardial fibroses, endomyocardial biopsies in DCM frequently reveal mononuclear cellular infiltrates, which, however, only in 20-25% of the cases may be regarded as chronic persisting myocarditis. The clinical and paraclinical findings in DCM and in the so-called latent cardiomyopathy are presented. In congestive heart failure, the best therapeutic results are achieved by the ACE inhibitors, along with vasodilator agents, digitalis glycosides and diuretics. Ultima ratio is the orthotopic heart transplantation, as it is only this intervention that will be able to improve the primarily bad prognosis decisively. Whether the treatment with immunosuppressive drugs exerts an influence upon the prognosis, has thus far remained an open question.
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PMID:[Dilated cardiomyopathy--heart muscle disease of unknown origin or an autoimmune disease? New aspects of etiology, pathogenesis and clinical practice]. 268 30

The criteria of the degree of hypertrophy and dilatation are defined. On this basis, functional and therapeutical regimen of regression of cardiac hypertrophy (prazosin, clonidine, nifedipine) are analyzed in concentric as well as in excentric hypertrophy in patients with arterial hypertension. Regression of cardiac hypertrophy is possible by differentiated pharmacotherapy, e. g., by prazosin, calciumantagonists, clonidine, alphamethyldopa, ACE-inhibitors as well as by combination therapies (beta-receptor blocking agents plus diuretics plus vasodilators). By these therapeutical measurements improvements in ventricular function can be achieved. Coronary reserve can be improved, consecutively the ischemic risk of hypertrophied cardiac muscle may be reduced. By the availability of pharmacotherapeutical regression of cardiac hypertrophy differentiated pharmacotherapy is possible in cardiac hypertrophy in man. Parallel to the regression improvement in ventricular function is possible. It remains still investigated, whether pharmacotherapeutical regression of cardiac hypertrophy is associated with decrease in coronary and late myocardial complications and whether prognosis of hypertensive heart disease can be significantly improved.
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PMID:[Progression and regression of heart hypertrophy in arterial hypertension: pathophysiology and clinical aspects]. 293 17

Preparation of sarcolemma from whole rabbit heart using the method of Jones et al. (Jones,L.R., Besch, H.R., Fleming, J.W., McConnaughey, M.M. and Watanabe, A.M. (1979) J. Biol. Chem. 254, 530-539) results in a 46-fold purification of the endothelial plasmalemma-specific marker angiotensin converting enzyme. This implies contamination of the sarcolemma with vascular endothelial plasmalemma. During preparation of sarcolemma from sheep heart, using the same method, angiotensin converting enzyme copurified with the general plasma membrane marker (Na+ + K+)-ATPase. The ratio of myocyte to endothelial plasma membrane in the final preparation is therefore similar to that in the whole heart homogenate. Ultrastructural analysis has shown that the myocyte/endothelial surface area is 70:30 in whole cardiac muscle. Comparison of angiotensin converting enzyme activity of an endothelial plasma membrane fraction with that of whole heart sarcolemma suggests an upper limit of 42% for endothelial contamination. Contamination by endothelial plasmalemma was dramatically reduced by preparing sarcolemma from myocytes produced by proteolytic disruption of whole hearts. Following disruption, myocytes were separated from non-muscle cells by sedimentation through 0.5 M sucrose. Sarcolemma prepared from sheep cardiac myocytes had approximately 15-fold less angiotensin converting enzyme activity than whole sheep heart sarcolemma but comparable ouabain-inhibitable (Na+ + K+)-ATPase activity.
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PMID:Contamination of a cardiac sarcolemmal preparation with endothelial plasma membrane. 300 68

Heart failure is defined as a malfunction of the cardiac muscle. The ongoing interaction between pump failure and the vasculature, however, results in symptoms due to malperfusion of the pulmonary and systemic circuit. As a consequence, biologic systems of pressure and volume control are activated. In the neurohumoral heart failure model the sympathetic nervous system, the renin system and endothelin all develop their own pathologic contribution to the disease process. Thereby the role of endothelin seems to be special since its production is particularly increased in advanced disease. Like angiotensin, endothelin has major proliferative properties to promote adverse vascular and myocardial growth. The finding of increasing neurohumoral activation as heart failure progresses and the role of plasma levels of neurohormones as predictors of mortality has rearranged the primary goal of therapy to suppress these deleterious neurohumoral systems as completely as possible. Though angiotensin converting enzyme inhibitors are currently first line therapy of heart failure, uncertainties remain concerning their mechanisms of action and - associated to that - optimal dosing.
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PMID:[Significance of neuroendocrine parameters in heart failure]. 965 97

We describe an interesting case of adenocarcinoma of the lung accompanying sarcoidosis with diffuse myocardial involvement. A 69-year-old man had a tumor shadow on chest X-ray films of the right upper lung field. Bronchofiberscopy was performed in Jan. 1997. Because transbronchial biopsy specimens disclosed granuloma, the patient was treated with isoniazid, rifampicin, and streptomycin sulfate for tuberculosis, but did not show any improvement. In March 1997, the patient was examined by an ophthalmologist for blurred vision. He was given a diagnosis of uveitis and referred to us for evaluation because his serum ACE and lysozyme levels were elevated. Bronchofiberscopy was performed again, and a diagnosis of lung cancer accompanying sarcoidosis was made based on the findings of transbronchial biopsy and bronchoalveolar lavage. The disease progressed rapidly, and the patient died 47 days after admission. Autopsy disclosed sarcoid granulomas in cardiac muscle tissue and lung tissue. There have been very few reports on the co-existence of sarcoidosis and lung cancer, and the relationship between the two diseases is unclear.
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PMID:[Lung cancer accompanying sarcoidosis with diffuse myocardial involvement]. 1006 64

The work has been done on primary heart culture from neonatal rat ventricle. Cardiomyocyte hypertrophy was modelled using noradrenaline (NA), angiotensin II (AII) and fetal serum, respectively. Cell hypertrophy of primary heart cultures was assessed by measuring the surface area, the scope of protein synthesis estimated by 3H-leucine autoradiography and the contents of nucleic acids in gallocyanin-chromalum stained cardiomyocytes. The structure of myofibrillar apparatus was studied by rhodamine-conjugated phalloidin and indirect immunofluorescence of muscle alpha-actinin. Treatment with 10(-6) M NA increased 3H-leucine incorporation in 9-day old heart culture by 42% without changing cell size. AII in a dose 1 microM stimulated protein synthesis activity by 1.3 fold and the surface area by 1.7 fold, both in 2- and 9-day old primary heart cultures. The maximum stimulation of cell hypertrophy was provided by the medium supplemented with fetal serum. RNA contents in the cytoplasm of cardiomyocytes increased by 7.8 fold and the myocardial cell size by 2.9 fold in serum-supplemented culture by 9 days of cultivation. In the medium with fetal serum, amounts of cardiomyocytes with tetraploid nuclei reached 33%, against 14% in control. Coculturing of myocardiocytes and fibroblasts rendered effects of fetal serum on the growth of myocardiocytes. Cultivation in the presence of 1 microM enalapril, an ACE inhibitor, suppressed the development of cardiac muscle cells hypertrophy. The effect of enalapril depended on the degree of cellular hypertrophy. Addition of 10 microM amiloride to the medium lowered the protein synthesis by 29% independently on the initial cellular hypertrophy.
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PMID:[Modelling of myocardial hypertrophy in vitro for solving problems of medicinal correction]. 1018 17


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