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 study was designed to clarify the effects of captopril (CAP) or nitrendipine (NITR) on cardiac hypertrophy and left ventricular expression of the laminin B2 or collagen (COL) gene in spontaneously hypertensive rats (SHRs). Cardiac weight was significantly increased in 20-week-old SHRs. Gene expression of the alpha 1 chain of type IV COL determined by northern blot analysis decreased with age in Wistar-Kyoto rats and SHRs. Left ventricular laminin B2 mRNA was decreased at 12 weeks and increased again at 20 weeks in both strains. Daily oral administration of CAP (40 mg/kg, n = 5) or NITR (30 mg/kg, n = 4) to SHRs from 8 to 20 weeks decreased blood pressure to 142 mmHg (p < 0.01 vs 197 mmHg in controls, n = 5). Cardiac weight was 1.26 +/- 0.04 (SE) g in controls and was reduced to 1.03 +/- 0.05 g (p < 0.01) by CAP, but not by NITR (1.24 +/- 0.04). Left ventricular laminin B2 gene expression was attenuated by CAP and NITR to 41% and 32% of the control value, respectively. CAP significantly decreased left ventricular alpha 1 type IV COL mRNA to 11% of the control level, whereas NITR caused a reduction only to 75%. CAP also decreased alpha 1 or alpha 2 type I COL mRNA. These results suggest that angiotensin converting enzyme inhibitors prevent and/or cause regression of cardiac hypertrophy by inhibiting the gene expression of extracellular matrix, and that angiotensin II may have a pivotal role in cardiac hypertrophy.
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PMID:Effects of captopril or nitrendipine on left ventricular collagen or laminin B2 gene expression. 816 45

An acute myocardial infarction (MI) is characterized by a change in the protein composition not only in the infarct area but, also, in the area not involved; the remodelling of cardiac tissue is the consequence of synthesis of qualitatively and quantitatively different collagenous and non-collagenous proteins. The authors discuss the biochemical and structural characteristics of extracellular space proteins (the main types of cardiac collagen include collagens I, III, IV and V, with an important role played by glycoproteins). The mechanisms involved in the alteration of the architecture of a left ventricle affected by an MI include the changed ratios of these proteins along with an effect on the structure and enzymatic activity of contractile proteins and myocyte slippage; these factors largely affect not only myocardial function but, also, the patient's prognosis. Despite a number of published data (mainly on the effect of ACE inhibitors), it is evident that the issue of controlling the quality and scar formation following an MI requires further study by clinical and experimental cardiologists.
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PMID:[The role of the myocardial interstitium in left ventricular remodeling after acute myocardial infarction]. 825 79

The cardiac interstitium is composed of non-myocyte cells embedded in a highly organized extracellular matrix containing a three-dimensional collagen network which serves to maintain the architecture of the myocardium and determines myocardial stiffness. In hypertensive heart disease, a heterogeneity in myocardial structure, created by the altered behaviour of cardiac fibroblasts responsible for collagen synthesis and degradation, can explain the appearance of diastolic and ultimately systolic dysfunction of the left ventricle. In vivo, circulating and myocardial renin-angiotensin systems (RAS) were found to be involved in the regulation of the structural remodelling of the cardiac interstitium. In vitro, in cultured adult rat cardiac fibroblasts, angiotensin II was shown to stimulate collagen synthesis and to inhibit collagenase activity, which is the key enzyme for collagen degradation. In the SHR-model of primary hypertension, left ventricular hypertrophy could be regressed and abnormal myocardial diastolic stiffness, due to interstitial fibrosis, could be restored to normal by inhibition of the myocardial RAS. These antifibrotic or cardioreparative effects of ACE inhibition that occurred irrespective of blood pressure normalization may be valuable in reversing left ventricular diastolic dysfunction in hypertensive heart disease.
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PMID:Renin-angiotensin system and myocardial fibrosis in hypertension: regulation of the myocardial collagen matrix. 828 64

Gelatinases are metalloproteinases in the kidney which can cleave type IV collagen as well as gelatin. We partially purified the 72 kDa and 92 kDa gelatinases. The gelatinolytic activity was measured by zymography and a quantitative biotin-avidin assay. By zymography, captopril in concentrations of 20 mM and 40 mM added to the incubation buffer reduced the gelatinolytic activity in a dose-dependent manner. The addition of zinc in a concentration of 50 to 100 microM reversed most of the inhibitory effect of captopril. By the biotin-avidin assay, captopril in a concentration of 30 to 50 nM reduced half of either the 72 kDa or 92 kDa gelatinolytic activity. Zinc in a concentration of 50 microM completely reversed the inhibitory effect of 1 microM captopril on both gelatinases. Lisinopril, a non-sulfhydryl ACE inhibitor, similarly inhibited the gelatinases, but a 100-fold higher concentration of the drug was needed. These findings suggest that captopril reversibly inhibits the 72 kDa and 92 kDa metalloproteinases by interacting with the zinc ion at their active sites. This inhibitory effect is observed with captopril levels comparable to the concentrations needed to inhibit the angiotensin converting enzyme in vivo and may at least partially explain some of the renoprotective effects seen with this drug.
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PMID:Captopril inhibits the 72 kDa and 92 kDa matrix metalloproteinases. 830 28

A review on the present knowledges of the myocardial structure, with particular emphasis on the collagen network and its degradation/synthesis process was performed. Myocardial fibrosis and cardiac remodeling concepts are analysed, explaining them in the context of ventricular hypertrophy, arterial hypertension, myocardial remodeling in ischemic heart disease and cardiac remodeling in the aged. We also review the role of the renin-angiotensin-aldosterone system in myocardial fibrosis, as well as the results of preventing action of angiotensin converting enzyme inhibitors and aldosterone antagonists in myocardial fibrosis and consequent cardiac remodeling in the animal experimentation. Clinical and therapeutic implications of this knowledge are discussed as well as therapeutic implication in man, in view of recent studies.
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PMID:[Myocardial fibrosis--the theoretical bases, clinical aspects and therapeutic implications]. 835 88

Cardiac hypertrophy in rats was produced by aortic banding for 6 weeks and regression of hypertrophy in these experimental animals was induced by administration of angiotensin converting enzyme inhibitor, enalapril (10 mg/kg/day) for 6 weeks. The left ventricular muscle mass and systolic pressure were decrease upon treating the hypertrophied rats with enalapril. This drug also decreased the number of alpha 1-adrenoceptors in hypertrophied myocardium without any changes in beta-adrenoceptors. The regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril for 10 weeks was not associated with any alterations in alpha 1-adrenoceptors in hypertrophied myocardium, but was decreased in beta-adrenoceptors. Effects of enalapril on extracellular matrix in the myocardium was also observed in regression of hypertrophy in which the type III collagen mRNA expression and collagen contents were reduced in comparison with those of hypertrophied myocardium. These results indicate that regression of cardiac hypertrophy is not always associated with a decrease in the number of alpha 1-adrenergic receptors and that the beneficial effects of enalapril in the hypertrophied heart in aortic banding animals may be of some specific nature.
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PMID:Effect of angiotensin converting enzyme inhibitor on regression in cardiac hypertrophy. 838

The myocardium contains a fibrillar collagen matrix that consists primarily of type I and type III collagens. There is a marked alteration in the ratio and amount of collagen phenotypes in myocardial hypertrophy due to pressure overload. The purpose of the present study is (1) to study the effect of antihypertensive therapy on collagen phenotypes, if instituted before development of hypertension in spontaneously hypertensive rat (SHR), and continued into adult life and (2) to study the effects of dissociation of hypertension from hypertrophy, on collagen phenotypes in SHRs. The present study shows the effect of two antihypertensive drugs, hydralazine and captopril, on collagen phenotypes in SHRs. Both hydralazine and captopril effectively controlled blood pressure in SHRs, but only captopril regressed hypertrophy and corrected the altered distribution of myocardial collagen phenotypes I and III. Untreated SHRs had a collagen type I:III ratio of 10.19 +/- 0.27, compared with that of 6.41 +/- 0.30 in normotensive WKY (P < 0.001). Captopril-treated SHRs had a collagen type I:III ratio of 6.75 +/- 0.37, which did not differ significantly from that in normotensive WKY. Hydralazine-treated SHRs had a collagen I:III ratio of 10.07 +/- 0.39, which is similar to the ratio in untreated SHRs. In normotensive rats, neither captopril nor hydralazine significantly altered collagen content or the ratio of type I:III collagen. Thus captopril, an angiotensin converting enzyme inhibitor, not only regressed hypertrophy but also reversed the altered distribution of type I and type III collagen whereas hydralazine which effectively controlled blood pressure, did not regress hypertrophy and did not correct the altered distribution in collagen phenotypes. These studies suggest that alteration of collagen phenotypes during hypertensive hypertrophy is independent of blood pressure control and myocardial mass.
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PMID:Alteration of cardiac collagen phenotypes in hypertensive hypertrophy: role of blood pressure. 847 26

1. The effects of the ACE inhibitor, captopril, on collagen metabolism in spontaneously hypertensive rats (SHR) with cardiac hypertrophy was examined. Captopril (100 mg/kg per day) was administered in drinking water to 20 week old male SHR for 12 weeks. Collagen concentration was calculated from hydroxyproline content, and relative proportions of types I, III and V collagen were determined by non-interrupted SDS-polyacrylamide gel electrophoresis (SDS-PAGE). These parameters were examined in age and sex matched Wistar-Kyoto (WKY) rats, as well as in non-treated SHR, and compared with those of captopril-treated SHR. 2. Captopril significantly reduced both blood pressure (191 +/- 12.1 vs 146 +/- 11.2 mmHg, P < 0.01), and the ratio of left ventricular (LV) weight to bodyweight (BW; 2.38 +/- 0.17 vs 2.05 +/- 0.12 mg/g, P < 0.01). There were no significant differences in collagen concentration among WKY rats, captopril-treated SHR and non-treated 32 week old SHR. However, total collagen content in captopril-treated SHR reduced significantly compared with non-treated 32 week old SHR (16.8 +/- 2.0 vs 21.3 +/- 0.8 mg, P < 0.01). The relative proportion of type V collagen was significantly higher in both captopril-treated (58.6 +/- 3.4 vs 46.8 +/- 1.3%, P < 0.01) and non-treated 32 week old SHR (59.9 +/- 3.1 vs 46.8 +/- 1.3%, P < 0.01) compared with WKY rats. However, there were no significant differences between captopril-treated SHR and non-treated 32 week old SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin converting enzyme inhibitor, captopril, inhibits cardiac hypertrophy without changing collagen types and concentration in spontaneously hypertensive rats. 848 25

Left ventricular hypertrophy constitutes an essential risk factor for sudden death, myocardial infarction and heart failure. The death rates of patients with ECG-demonstrated cardiac hypertrophy are 4.8 times as high as those of healthy subjects. Cardiac hypertrophy is associated with a substantially increased incidence of ventricular arrhythmias. The condition is treatable in most patients. While the most effective group of drugs for controlling cardiac hypertrophy are ACE inhibitors; methyldopa, calcium antagonists, and beta-blockers have also proved useful in the management of cardiac hypertrophy in hypertension. Diuretics other than indapamide are not appropriate for treating cardiac hypertrophy. An additional benefit of ACE inhibitor administration is they can favourable affect increased levels of collagen in the hypertrophic myocardium. The prognosis of hypertensive patients, whose treatment has lead to regression in cardiac hypertrophy in hypertension, is markedly better than that of patients in whom regression fails to be achieved. A role in the development of cardiac hypertrophy in hypertension, in addition to the blood pressure level, is played by a number of mechanisms; it is the genetic factor which has received most attention recently. As the prognosis of hypertrophic patients has been found to correlate more closely with left ventricular weight, determined by echocardiography, than with blood pressure, echocardiography should be employed more often in the future to help optimize antihypertensive therapy.
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PMID:[Cardiac hypertrophy in hypertension--clinical significance and possibilities of control]. 850 Mar

The interstitial space of the myocardium is composed of nonmyocyte cells and a highly organized collagen network which serves to maintain the architecture and mechanical behavior of the myocardial walls. It is the myocardial collagen matrix that determines myocardial stiffness in the normal and structurally remodeled myocardium. In hypertensive heart disease, the heterogeneity in myocardial structure, created by the altered behavior of nonmyocyte cells, particularly cardiac fibroblasts which are responsible for collagen synthesis and degradation, explains the appearance of diastolic and/or systolic dysfunction of the left ventricle that leads to symptomatic heart failure. Several lines of evidence suggest that circulating and myocardial renin-angiotensin systems (RAS) are involved in the regulation of the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition that was found to prevent myocardial fibrosis in the rat with renovascular hypertension. In cultured adult rat cardiac fibroblasts angiotensin II was shown to directly stimulate collagen synthesis and to inhibit collagenase activity, which is the key enzyme for collagen degradation, that would lead to collagen accumulation. In the spontaneously hypertensive rat, an appropriate experimental model for primary hypertension in man, left ventricular hypertrophy could be regressed and abnormal myocardial diastolic stiffness due to interstitial fibrosis could be restored to normal by inhibition of the myocardial RAS. These antifibrotic or cardioreparative effects of ACE inhibition that occurred irrespective of blood pressure normalization may be valuable in reversing left ventricular diastolic dysfunction in hypertensive heart disease.
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PMID:Renin-angiotensin system and myocardial collagen matrix remodeling in hypertensive heart disease: in vivo and in vitro studies on collagen matrix regulation. 851 39


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