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)

Lisinopril is an angiotensin converting enzyme inhibitor used in the treatment of cardiovascular disease. We report a case of pemphigus foliaceus in a 66-year-old male treated with lisinopril for hypertension and a previous myocardial infarction. The drug-induced variant of pemphigus is caused by a wide variety of drugs and is most frequently associated with captopril and penicillamine. It has not previously been reported in this commonly used drug.
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PMID:Pemphigus foliaceus: an adverse reaction to lisinopril. 1475 54

During cardiac surgery, as a result of surgical aggression, myocardial ischaemia and cardiopulmonary bypass, the renin-angiotensin-aldosterone mechanism is intensely activated. Our aim is to document whether, in the case of patients undergoing chronic treatment with lisinopril, the non-withdrawal of this inhibitor's administration before cardiac surgery and the administering of a last dose on the day of the operation are associated with coronary haemodynamic alterations. A study was made of 18 patients submitted to myocardial revascularization under extracorporeal circulation and distributed in two groups: group A) without ACE inhibitorsplacebo, group B) with ACE inhibitors (Lisinopril). Coronary blood flow (CBF) was determined by inverted thermodilution via Baim's catheter. Coronary and metabolic haemodynamic values were calculated. Lisinopril had no significant influence on the CBF or on the other above-mentioned values. Therefore, it is not necessary to withdraw ACE inhibitors in cardiac surgery interventions.
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PMID:[Evaluation of the withdrawal of ACE inhibitors in coronary artery surgery]. 1534 63

ACE inhibitors have significantly decreased cardiovascular mortality, myocardial infarction (MI), and hospitalizations for heart failure (HF) in patients with asymptomatic or symptomatic left ventricular (LV) systolic dysfunction. Furthermore, the extended 12-year study of the SOLVD (Studies Of Left Ventricular Dysfunction) Prevention and Treatment trials (X-SOLVD) demonstrated a significant benefit with a reduction of cumulative all-cause death compared with placebo (50.9% vs 56.4%) [hazard ratio (HR) 0.86; 95% CI 0.79, 0.93; p < 0.001]. The survival benefits and significant reductions in cardiovascular morbidity related to treatment with ACE inhibitors are likely achieved by titrating the dose of ACE inhibitors to the target dose achieved in clinical trials. Although the ATLAS (Assessment of Treatment with Lisinopril And Survival) study, which randomly allocated HF patients to low- or high-dose lisinopril, showed no significant difference between groups for the primary outcome of all-cause mortality (HR 0.92; 95% CI 0.82, 1.03), the predetermined secondary combined outcome of all-cause mortality and HF hospitalization was reduced by 15% for the patients receiving high-dose lisinopril compared with low-dose (p < 0.001) with a 24% reduction in HF hospitalization (p = 0.002). Despite the use of ACE inhibitors, blockade of the renin angiotensin aldosterone system (RAAS) remains incomplete, with evidence of continued production of angiotensin II by non-ACE-dependent pathways. The safety and potential benefits of angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) in patients with impaired systolic function have been assessed in moderate to large clinical trials. In patients with impaired LV systolic function and HF, combination therapy with ARBs with recommended HF therapy including ACE inhibitors in patients who remain symptomatic may be considered for its morbidity benefit. Based on the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity)-Added data, candesartan cilexetil in addition to standard HF therapy results in a further reduction of cardiovascular mortality. Close monitoring of renal function and serum potassium levels is needed in this setting. The VALIANT (VALsartan In Acute myocardial iNfarction Trial) results suggest that valsartan is as effective as captopril in patients following an acute MI with HF and/or LV systolic dysfunction and may be used as an alternative treatment in ACE inhibitor-intolerant patients. There was no survival benefit with valsartan-captopril combination compared with captopril alone in this trial. Despite these results, ACE inhibitors remain the first-choice therapeutic agent in post-MI patients, and ARBs can be used in patients with clear intolerance. Although the use of ACE inhibitors may be appealing in patients with HF and preserved LV systolic function, there is currently no evidence from large clinical trials to support this.
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PMID:ACE inhibitors in heart failure: what more do we need to know? 1625 23

The role of ACE inhibitors (Lisinopril) in reproductive function remains controversial. Some benefits seem to be derivable even in non-hypertensive males with low doses. This study was done using rat model to establish this fact. Male rats were divided into different groups to receive different doses of lisinopril. A control group received no drugs. The mean arterial pressure fell the most with 5 mg of lisinopril. The greatest increase in sperm count and motility was recorded for this same group. This response was dose dependent, falling as the drug dose fell. Lisinopril appeared to, in a dose dependent manner, improve sperm count and motility. In low doses, there is no significant change in arterial pressure. Infertile males with poor quality semen could benefit from a low dose of ACE inhibition. Where they are also hypertensive, ACE inhibition would be an appropriate first line treatment.
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PMID:Effect of lisnopril, an angiotensin converting enzyme (ACE) inhibitor on spermatogenesis in rats. 1657 3

To characterize the inhibitory specificity of angiotensin converting enzyme (ACE) inhibitors for matrix metalloproteinase 9 (MMP-9) activity, molecular modeling of these complex was performed referring the recent X-ray structure analyses using lisinopril as an ACE inhibitor. Two interaction modes differing in the orientation of the inhibitor on the active site were identified. Lisinopril was effectively stabilized by specific hydrogen bonds and hydrophobic interactions in the active site of MMP-9, and its hydrophobic group appeared to interact preferentially with the S1 site compared with the S1' site. These findings showed that ACE inhibitors could become important seeds for cardiovascular protection and the development of MMP inhibitors.
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PMID:Prediction of interaction mode between a typical ACE inhibitor and MMP-9 active site. 1727 82

The effects of hypotensive agents (captopril, enalaprilate, and lisinopril) on the activities of components of the fibrinolytic system (FS) and the effects of antifibrinolytic agents (6-aminohexanoic acid (6-AHA) and tranexamic acid (t-AMCHA)) on the activities of angiotensin converting enzyme (ACE) were studied in vitro. Enalaprilate did not affect the FS activity. Captopril considerably inhibited the amidase activities of urokinase (u-PA), plasminogen tissue activator (t-PA), and plasmin ([I]50 (2.0-2.6) +/- 0.1 mM), and the activation of Glu-plasminogen affected by t-PA and u-PA ([I]50 (1.50-1.80) +/- 0.06 mM), which may be due to the presence of a mercapto group in the inhibitor molecule. Lisinopril did not affect the amidase activities of FS enzymes, but stimulated Glu-plasminogen and u-PA activation and inhibited activation of t-PA-fibrin-bound Glu-plasminogen ([I]50 (12.0 +/- 0.5) mM). Presumably, these effects can be explained by the presence in lisinopril of a Lys side residue, whose binding to lysine-binding Glu-plasminogen centers resulted, on the one hand, in the transformation of its closed conformation to a semi-open one and, on the other hand, in its desorption from fibrin. Unspecific inhibition of the activity of ACE, a key enzyme of the renin-angiotensin system, in the presence of 6-AHA and t-AMCHA ([I]50 10.0 +/- 0.5 and 7.5 +/- 0.4 mM, respectively) was found. A decrease in the ACE activity along with the growth of the fibrin monomer concentration was revealed. The data demonstrate that, along with endogenous mediated interactions, relations based on the direct interactions of exogenous inhibitors of one system affecting the activities of components of another system can take place.
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PMID:[The in vitro cross-effects of inhibitors of renin-angiotensin and fibrinolytic systems on the key enzymes of these systems]. 1869 19

Lisinopril, an angiotensin converting enzyme (ACE) inhibitor drug, was encapsulated in poly(lactide-co-glicolide) (PLGA) nanoparticles (NP) for site-specific delivery by catheters in prevention of restenosis. NP were prepared by emulsification-diffusion method. The PLGA type, stabilizing agent type and its concentration were studied as process variables. The z-average particle size varied between 265-412 nm. The highest zeta potential was seen in NP prepared with Pluronic F-68. None of the studied variables or their interactions had a significant effect on the particle size while all had main effect on the zeta potential. The highest entrapment efficiency was 93% and all studied variables and their interactions except PLGA type and its interaction with the stabilizer type had significant effects on the loading. Baker-Lonsdale model was the most appropriate model for release of lisinopril from NP. Five per cent PLGA 75:25 and 5% Pluronic F-68 showed promising results for 21 days release of lisinopril as an anti-restenotic agent.
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PMID:Production and in vitro characterization of lisinopril-loaded nanoparticles for the treatment of restenosis in stented coronary arteries. 1923 23

In humans, the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene accounts for half of the variance in plasma ACE activity. The deletion allele is associated with high plasma ACE activity, cardiovascular disease, and renal disease. In rat, a similar association is found between the B and L alleles of a microsatellite marker in the ACE gene. We identified the B/L variation in the Wistar outbred rat and bred two lines homozygous for the two alleles (WU-B and WU-L). ACE activity was measured in serum, heart, kidney, and aorta homogenates. Immunohistochemistry and ACE mRNA expression were performed in heart, kidney, and aortic tissue. Aortic rings were collected and stimulated with AngI, AngII, and AngI with Lisinopril to measure ACE functional activity by vasoconstrictor response. Serum, heart, and kidney ACE activity and kidney mRNA expression were two-fold higher in WU-B. Kidney staining showed a clear difference in tubular ACE expression, with more staining in WU-B. While in aorta ACE activity and mRNA expression was twofold higher in WU-L, functional conversion of AngI was higher in WU-B, indicating either a functional difference in AngI to AngII conversion between the two alleles due to different splicing or the presence of other factors involved in the conversion that are differentially expressed as the result of differences in the ACE alleles. The newly developed WU-B and WU-L lines show tissue-specific differences in ACE expression and activity. This provides an experimental tool to study the pathophysiologic consequences of differences in ACE alleles in renal and cardiovascular disease.
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PMID:Differential ACE expression among tissues in allele-specific Wistar rat lines. 1925 5

A series of new 3-mercapto-2-methyl-propanoyl-pyrrolidine derivatives (V, VIa-e) were designed. A new validated ACE inhibitors pharmacophore model (hypothesis) was generated for the first time in this research from the biologically active (frozen) conformation of Lisinopril-Human ACE complex that was downloaded from PDB, using stepwise technique of CATALYST modules. The molecular modeling compare-fit study of the designed molecules (V, VIa-e), with such ACE inhibitors hypothesis was fulfilled, and several compounds showed significant high simulation fit values. The compounds with high fit values were synthesized and biologically evaluated in vivo as hypotensive agents. It appears that the in vivo hypotensive activity of compounds V, VIa, VIb, and VIe was consistent with their molecular modeling results, and compound VIe showed the highest activity in comparison to Captopril.
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PMID:ACE inhibitors hypothesis generation for selective design, synthesis and biological evaluation of 3-mercapto-2-methyl-propanoyl-pyrrolidine-3-imine derivatives as antihypertensive agents. 1940 13

Acute myocardial infarction (AMI) remains the leading cause of mortality in the world. Early intervention using salvianolic acids (SA) can substantially improve clinical outcomes. However, in spite of the great achievements that have been made in elucidating the protective effects of SA on AMI, the effects of SA on the contractile performance of the left ventricle (LV) and the underlying mechanism are still not so clear. In the present study, AMI was introduced by ligation of the left anterior descending coronary artery near the main pulmonary artery. Administration of SA significantly decreased infarct size, improved LV function and appearance of the myocardium and decreased myocardial malondialdehyde levels compared with the AMI group. Furthermore, treatment with SA significantly downregulated the mRNA expression level and activity of matrix metalloproteinase-9 (MMP-9), but did not regulate the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression level at the infarct area. Lisinopril (an angiotensin converting enzyme inhibitor), which holds potential effects on cardioprotection, was chosen as the positive control in this study. Lisinopril elevated LV function and appearance of the myocardium, decreased malondialdehyde levels without an influence on infarct size, and regulated the MMP-9 enzyme level but not the MMP-9 mRNA and TIMP-1 protein levels. These findings suggest that early SA treatment is effective to improve LV function; and SA may exert preventative effects against myocardial remodeling after infarction.
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PMID:Cardioprotection and matrix metalloproteinase-9 regulation of salvianolic acids on myocardial infarction in rats. 1943 Nov


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