muramidase and Myocardial-Infarction

Topics: Alcoholism; Aminopeptidases; Amylases; Aspartate Aminotransferases; Cholinesterases; Creatine Kinase; Cystic Fibrosis; Enzyme Activation; Enzymes; Female; gamma-Glutamyltransferase; Half-Life; Humans; Isoenzymes; L-Lactate Dehydrogenase; Liver Cirrhosis; Liver Neoplasms; Muramidase; Myocardial Infarction; Pepsinogens; Phenobarbital; Porphyrias; Pregnancy

Topics: Aminopeptidases; Amylases; Anaphylaxis; Animals; Catalase; Clinical Laboratory Techniques; Deoxyribonucleases; Diuresis; Enzyme Activation; Enzyme Inhibitors; Enzymes; Esterases; Fibrinolytic Agents; Glycoside Hydrolases; Humans; Kallikreins; Kidney Diseases; L-Lactate Dehydrogenase; Muramidase; Myocardial Infarction; Pepsinogens; Phosphoric Monoester Hydrolases; Proteinuria; Rats; Ribonucleases; Sulfatases; Transaminases; Water-Electrolyte Balance

Heart failure (HF) ensuing myocardial infarction (MI) is characterized by the initiation of a systemic inflammatory response. We aimed to elucidate the impact of myelomonocytic cells and their activation by angiotensin II on vascular endothelial function in a mouse model of HF after MI.. HF was induced in male C57BL/6J mice by permanent ligation of the left anterior descending coronary artery. Compared to sham, HF mice had significantly impaired endothelial function accompanied by enhanced mobilization of Sca-1+c-Kit+ haematopoietic stem cells and Sca-1-c-Kit+ common myeloid and granulocyte-macrophage progenitors in the bone marrow as well as increased vascular infiltration of CD11b+Ly6G-Ly6Chigh monocytes and accumulation of CD11b+ F4/80+ macrophages, assessed by flow cytometry. Using mice with Cre-inducible expression of diphtheria toxin receptor in myeloid cells, we selectively depleted lysozyme M+ myelomonocytic cells for 10 days starting 28 days after MI. While the cardiac phenotype remained unaltered until 38 days post-MI, myeloid cell depletion attenuated vascular accumulation of Nox2+CD45+ cells, endothelial dysfunction, oxidative stress, and vascular expression of adhesion molecules and angiotensin II receptor type 1 (AT1R). Pharmacological blockade of this receptor for 4 weeks did not significantly alter cardiac function, but mimicked the effects of myeloid cell depletion: telmisartan (20 mg/kg/day, fed to C57BL/6J mice) diminished bone marrow myelopoesis and myeloid reactive oxygen species production, attenuated endothelial leucocyte rolling and vascular accumulation of CD11b+Ly6G-Ly6Chigh monocytes and macrophages, resulting in improved vascular function with less abundance of Nox2+CD45+ cells.. Endothelial dysfunction in HF ensuing MI is mediated by inflammatory Nox2+ myeloid cells infiltrating the vessel wall that can be targeted by AT1R blockade.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Animals, Genetically Modified; Disease Models, Animal; Endothelial Cells; Heart Failure; Leukocyte Rolling; Macrophages; Male; Mice, Inbred C57BL; Monocytes; Muramidase; Myeloid Cells; Myocardial Infarction; NADPH Oxidase 2; Oxidative Stress; Receptor, Angiotensin, Type 1; Signal Transduction; Telmisartan; Vasculitis

Myelomonocytic cells are critical in injury and healing post-myocardial infarction (MI). Mechanisms of regulation, however, are incompletely understood. The aim of the study was to elucidate the role of interferon gamma (IFN-γ) in the orchestrated inflammatory response in a murine model of MI.. MI was induced in 8- to 12-week-old male mice (C57BL/6 background) by permanent ligation of the left anterior descending (LAD) coronary artery. Lysozyme M (LysM)+ cell-depleted LysMiDTR transgenic mice displayed a reduced influx of CD45.2+/CD3-/CD11b+/Gr-1high neutrophils into infarcted myocardium 1 day post-MI compared with infarcted controls, paralleled by decreased cardiac mRNA levels of IFN-γ and tumour necrosis factor alpha (TNF-α). Mortality after MI was significantly increased in LysM+ cell-depleted mice within 28 days post-MI. To more specifically address the role of neutrophils, we depleted C57BL/6 mice with a monoclonal anti-Gr-1 antibody and found increased mortality, deteriorated cardiac function as well as decreased cardiac IFN-γ mRNA expression early after MI. Ccl2, Cxcl1, Cx3cl1, and Il12b mRNA were reduced 3 days after MI, as was the amount of CD11b+/Ly-6G-/Ly-6Chigh inflammatory monocytes. LAD-ligated Cramp-/- mice lacking cathelicidin important in neutrophil-dependent monocyte chemotaxis as well as IFNγ-/- and TNFα-/- mice phenocopied Gr-1+ cell-depleted mice, supporting a regulatory role of IFN-γ impacting on both the sequence of inflammatory cell invasion and cardiac outcome early after MI. The use of conditional IFN-γ receptor deficient mice indicated a direct effect of IFN-γ on LysM+ cells in cardiac injury post-MI. Using IFN-γ reporter mice and flow cytometry, we identified cardiac lymphoid cells (CD4+ and CD8+ T cells and natural killer cells) as primary source of this cytokine in the cardiac inflammatory response post-MI.. IFN-γ directs a sequential chemotactic cellular immune response and determines survival and cardiac function post-MI.

Topics: Animals; Antimicrobial Cationic Peptides; Cathelicidins; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chemotaxis, Leukocyte; Disease Models, Animal; Immunity, Cellular; Interferon gamma Receptor; Interferon-gamma; Killer Cells, Natural; Lymphocytes; Male; Mice, Inbred C57BL; Mice, Knockout; Muramidase; Myocardial Infarction; Myocardium; Receptors, Interferon; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha

Coronary heart disease (CHD) is a major killer worldwide. Atherosclerosis, which is the basis of CHD, is believed to be an inflammatory disorder. Though various aspects of atherosclerosis are extensively studied, leukocytic hydrolytic enzymes are not studied very well with respect to CHD.. This study was planned to assess changes associated with leukocytic hydrolases in CHD patients.. A tertiary care hospital; case-control study.. 106 patients with acute myocardial infarction, 60 patients with unstable angina and 45 healthy controls were included in the study. Acid phosphatase, lysozyme, adenosine deaminase (ADA) and cathepsin-G levels were estimated from leukocytes. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured.. Statistical comparison of data was done using student's t-test (unpaired). Correlation difference was calculated by using Pearson correlation coefficient.. Significantly higher levels of acid phosphatase, lysozyme, ADA with lower levels of cathepsin G in leukocytes were observed in CHD group. We also found significantly higher levels of serum MDA with lower concentrations of blood GSH in CHD group. In diabetic CHD group, significantly higher levels of leukocytic acid phosphatase, lysozyme, ADA and serum MDA with lower levels of cathepsin G and blood GSH were observed.. Our study indicates that leukocyte hydrolytic enzymes, mainly acid phosphatase, lysozyme and ADA were more active in CHD patients and may contribute to inflammation related with CHD. Its also indicates that leukocyte cathepsin-G may have antiinflammatory role.

Topics: Acid Phosphatase; Acute Disease; Adult; Angina, Unstable; Cathepsin G; Cathepsins; Coronary Disease; Female; Humans; Leukocytes; Male; Malondialdehyde; Middle Aged; Muramidase; Myocardial Infarction; Serine Endopeptidases

Changes of systemic immune status, involved in the immunopathogenesis of atherosclerosis, have been identified in patients with unstable angina pectoris. The developing acute myocardial infarction is accompanied by the formation of a myocardial aseptic inflammatory focus, from which biologically active products are absorbed, resulting in additional immunologic shifts. A differential diagnosis algorithm has been evolved on the basis of the comparison of a series of biochemical and immunologic parameters in patients with unstable angina, investigated at the peak of its clinical manifestations, and those with acute myocardial infarction.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Antigen-Antibody Complex; Diagnosis, Differential; Humans; Leukocyte Count; Lipids; Male; Middle Aged; Muramidase; Myocardial Infarction; Phagocytosis

Topics: Adult; Aged; Granulocytes; Hemolysis; Humans; Middle Aged; Muramidase; Myocardial Infarction

Topics: Adult; Aged; Heparin; Humans; Middle Aged; Muramidase; Myocardial Infarction

The activity of N-acetyl-beta-glucosaminidase (NAG) was found to be increased in serial plasma samples from patients with acute myocardial infarction (AMI). Maximum activity occurred 18 hr after the onset of chest pain, and a further peak of activity was found at 72 hr. Four isozymes of NAG were resolved from samples of human myocardium. All four isozymes were present in plasma from patients with AMI but not in normal plasma. beta-Glucuronidase, which is also present in myocardium, had increased activity in plasma at 18 hr but not at 72 hr in patients with AMI. Lysozyme, a lysosomal enzyme in white blood cells, had increased activity in plasma at 72 hr. There was a linear relationship (r = 0.98) between peak levels of NAG at 18 hr and the peak activity of the MB-isozyme of creatine kinase (CK-MB). Three groups of 10 patients were treated with drugs known to stabilize lysosomes during experimental myocardial anoxia. The first group received 25 mg/kg methylprednisolone sodium succinate i.v. within 4 hr of the onset of chest pain. The second group received propranolol, 5-mg, i.v. within 4 hr of the onset of chest pain. The second group received propranolol, 5-mg, i.v. within 4 hr of the onset of chest pain, and the third group comprised patients who developed AMI while on propranolol therapy and were maintained on this drug after admission to the hospital. All three groups showed an alteration in the pattern of lysosomal and cytosolic enzyme activity and a relative reduction in NAG activity compared to CK-MB.

Topics: Acetylglucosaminidase; Adult; Creatine Kinase; Female; Hexosaminidases; Humans; Isoenzymes; Lysosomes; Male; Methylprednisolone Hemisuccinate; Middle Aged; Muramidase; Myocardial Infarction; Propranolol

Topics: Aminopeptidases; Analysis of Variance; Cholestasis; Diagnostic Techniques and Procedures; Enzymes; Fatty Liver; Female; Glucuronidase; Humans; Leukemia, Myeloid; Male; Muramidase; Myocardial Infarction; Phosphorylases; Pregnancy; Pregnancy Tests

N-acetyl-beta-glucosaminidase (EC 3.2.1.30, recommended name beta-N-Acetylglucosaminidase) was found to be a constituent of human cardiac lysosomes. beta-glucuronidase was also found in this tissue, while lysozyme, an enzyme present in leucocyte lysosomes, was not detectable in the heart. The activities of both N-acetyl-beta-glucosaminidase and beta-glucuronidase were elevated in plasma during the first 24 h after the onset of chest pain in patients with acute myocardial infarction and the peak levels of N-acetyl-beta-glucosaminidase correlated well with those of creatine kinase. N-acetyl-beta-glucosaminidase showed a further rise in plasma activity which gave a peak at 72 h after the onset of chest pain and this was accompanied by a rise in lysozyme activity. It is suggested that lysosome disruption caused by myocardial cell necrosis was responsible for the initial rise in plasma lysosomal enzyme activity and that the subsequent inflammatory reaction gave rise to the second peak.

Topics: Acetylglucosaminidase; Acute Disease; Creatine Kinase; Female; Glucuronidase; Hexosaminidases; Humans; Isoenzymes; Lysosomes; Male; Muramidase; Myocardial Infarction; Myocardium; Subcellular Fractions

On the assumption that increased urinary lysozyme concentration (;lysozymuria') indicates tubular proteinuria and therefore impaired tubular function, urinary lysozyme has been estimated in acute disorders where transient disturbances of renal function might be expected, in cases diagnosed clinically as extrarenal uraemia, and in a few examples of acute renal disease. Reversible lysozymuria occurred with hypokalaemia, postoperative ;collapse', electrolyte depletion, severe extrarenal infection, acute pyelonephritis, the nephrotic syndrome, after a few apparently uncomplicated surgical operations, and very transiently after ventricular fibrillation abolished by DC shock. There was no lysozymuria with severe uraemic heart failure, aspirin and paracetamol poisoning, or severe jaundice, nor in two cases of acute glomerulonephritis. Although lysozymuria may occasionally be useful in the clinical diagnosis of acutely disordered renal function, the results suggest that its value is limited; on the other hand, they have provided information on renal pathophysiology in acute disease.

Topics: Acetaminophen; Acute Disease; Aspirin; Electroshock; Glomerulonephritis; Heart Failure; Humans; Hypokalemia; Jaundice; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Tubules; Muramidase; Myocardial Infarction; Nephrotic Syndrome; Pneumonia; Postoperative Complications; Proteinuria; Pyelonephritis; Uremia; Ventricular Fibrillation

Topics: Humans; Muramidase; Myocardial Infarction