acid-phosphatase and Vascular-Diseases

Clinical and experimental studies demonstrate the important roles of vascular smooth muscle cells (VSMC) in the pathogenesis of atherosclerosis. We have previously determined that the osteogenic transcription factor Runx2 is essential for VSMC calcification. The present study characterized Runx2-regulated signals and their potential roles in vascular calcification.. In vivo studies with atherogenic apolipoprotein E(-/-) mice demonstrated that increased oxidative stress was associated with upregulation of Runx2 and receptor activator of nuclear factor κB ligand (RANKL), which colocalized in the calcified atherosclerotic lesions and were juxtaposed to infiltrated macrophages and osteoclast-like cells that are positively stained for an osteoclast marker, tartrate-resistant acid phosphatase. Mechanistic studies using RNA interference, a luciferase reporter system, chromatin immunoprecipitation, and electrophoretic mobility shift assays indicated that Runx2 regulated the expression of RANKL via a direct binding to the 5'-flanking region of the RANKL. Functional characterization revealed that RANKL did not induce VSMC calcification, nor was RANKL required for oxidative stress-induced VSMC calcification. Using a coculture system, we demonstrated that VSMC-expressed RANKL induced migration as well as differentiation of bone marrow-derived macrophages into multinucleated, tartrate-resistant acid phosphatase-positive osteoclast-like cells. These effects were inhibited by the RANKL antagonist osteoprotegerin and with VSMC deficient in Runx2 or RANKL.. We demonstrate that Runx2 directly binds to the promoter and controls the expression of RANKL, which mediates the crosstalk between calcifying VSMC and migration and differentiation of macrophages into osteoclast-like cells in the atherosclerotic lesions. Our studies provide novel mechanistic insights into the regulation and function of VSMC-derived RANKL in the pathogenesis of atherosclerosis and vascular calcification.

Topics: Acid Phosphatase; Animals; Atherosclerosis; Calcinosis; Cell Differentiation; Cell Movement; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Isoenzymes; Macrophages; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Osteoclasts; Oxidative Stress; Promoter Regions, Genetic; Protein Binding; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Vascular Diseases

We describe a patient with a radiologically verified inferior vena cava obstruction due to metastatic adenocarcinoma of the prostate who was treated by orchiectomy. The prompt regression of the disease causing the obstruction confirms that orchiectomy alone can be an effective treatment of massive, functionally significant metastatic carcinoma of the prostate.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Edema; Humans; Male; Orchiectomy; Prostatic Neoplasms; Tomography, X-Ray Computed; Vascular Diseases; Vena Cava, Inferior

A rapid radioassay was used to characterise the adenosine diphosphatase (ADPase) activities in human plasma. There was a major peak at pH 9.3, 80% of whose activity was attributable to non-specific alkaline phosphatase, with the remaining 20% probably due to a specific ADPase. There was also a small peak of ADPase activity at pH 4.0. Inhibitor and chromatographic studies showed that whilst much of this activity was attributable to non-specific acid phosphatase, there was a discrete acid ADPase. Assays of plasma ADPase activities in vascular disorders, including myocardial infarction, peripheral vascular disease and diabetes mellitus, reveal no alterations from control values. Activities of alkaline ADPase were elevated in both chronic and acute liver failure. Acid ADPase was also increased in chronic liver disease and it is suggested that alterations in ADPase activities in liver disorders may contribute to the haemostatic problems observed in these patients.

Topics: Acid Phosphatase; Acute Disease; Alkaline Phosphatase; Apyrase; Chromatography, Gel; Chronic Disease; Humans; Hydrogen-Ion Concentration; Kinetics; Liver Diseases; Myocardial Infarction; Phosphoric Monoester Hydrolases; Vascular Diseases

Topics: Acid Phosphatase; Adult; Brain Neoplasms; Central Nervous System Diseases; Cerebrospinal Fluid; Child, Preschool; Epilepsy; Female; Glioblastoma; Humans; Hypersensitivity; Inflammation; Lymphoma, Large B-Cell, Diffuse; Lysosomes; Male; Mental Disorders; Neurotic Disorders; Peptide Hydrolases; Psychotic Disorders; Vascular Diseases

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Femoral Artery; Femoral Vein; Glutamate Dehydrogenase; Guinea Pigs; Histocytochemistry; Ischemia; L-Lactate Dehydrogenase; Ligation; Malate Dehydrogenase; Succinate Dehydrogenase; Vascular Diseases

Topics: Acid Phosphatase; Agglutination Tests; Antibodies; Antigen-Antibody Complex; Arthus Reaction; Complement Fixation Tests; Complement System Proteins; Humans; Immune Adherence Reaction; Neutrophils; Peptide Hydrolases; Pharynx; Respiratory Tract Infections; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Vascular Diseases