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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta 1 integrin adhesion receptors mediate the binding of cells to extracellular matrices, facilitating their growth, migration, and capacity to deposit matrix proteins: important factors in arterial restenosis and atherosclerosis. The expression of integrins in human coronary artery is, however, unexplored. The aim of the current study was, therefore, to define the expression of beta 1 integrins by cultured human coronary artery vascular smooth muscle cells (hCAVSMC) and in normal human coronary artery; confirming whether or not this differs from the repertoire found in other species and human vessels. The expression of beta 1 integrins by hCAVSMC was assessed by immuno-precipitation and the alkaline phosphatase anti-alkaline phosphatase (APAAP) immunochemical technique. In addition, mRNA expression was defined by reverse transcription polymerase chain reaction (RT-PCR). Normal adult human coronary arteries (n = 4) were also stained by the APAAP method. In vitro hCAVSMC express alpha 2 beta 1 (a collagen and occasional laminin receptor) and alpha 5 beta 1 (a fibronectin receptor) with lesser expression of alpha 3 beta 1 (a multifunctional receptor). They do, however, possess mRNA for several other integrins. Cells within the media of human coronary artery wall express alpha 3 beta 1 and alpha 5 beta 1 but not alpha 2 beta 1: instead the alternative collagen/laminin receptor, alpha 1 beta 1, is expressed in vivo. This pattern of expression differs subtly from that described in rats through it closely parallels that found in other human arteries.
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PMID:The expression of beta 1 integrins in human coronary artery. 978 72

Vascular calcification is a frequent component of atherosclerosis, yet the pathological mechanisms that regulate its formation are poorly understood. Calcification of the vessel wall may represent a process by which cells that normally exhibit a smooth muscle phenotype differentiate into cells that exhibit an osteoblast-like phenotype. One of the determinants of cellular phenotype is extracellular matrix; thus, we undertook the current study to evaluate the influence of extracellular matrix on calcification of vascular cells in vitro. Cell lines derived from bovine aortic media were divided into 1 of 3 groups: those that did not mineralize, those that mineralized slowly, or those that mineralized rapidly. When slowly mineralizing cells were plated onto matrix produced by rapidly mineralizing cells, the time required for mineralization decreased from 33+/-3.0 days to 7.8+/-1.3 days. Matrix produced by rapidly mineralizing cells was found to contain 3 times the amount of collagen I and fibronectin but 70% less collagen IV than nonmineralizing clones. When slowly mineralizing cells were cultured on purified collagen I or fibronectin, mineralized nodule formation, calcium incorporation, von Kossa staining, and alkaline phosphatase activity increased. In contrast, culturing slowly mineralizing cells on purified collagen IV inhibited these mineralization parameters. Furthermore, blocking antibodies to alpha5 integrins significantly inhibited the fibronectin-mediated increases in alkaline phosphatase activity, indicating that integrin-based signaling may be involved. These data suggest that matrix composition can regulate development of arterial calcification and that a subpopulation of vascular cells preferentially produces positively regulating matrix components.
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PMID:Fibronectin and collagen I matrixes promote calcification of vascular cells in vitro, whereas collagen IV matrix is inhibitory. 984 91

Calcification of vascular tissue is a common complication in aging, atherosclerosis, diabetes, renal failure, aortic stenosis, and prosthetic valve replacement. Osteopontin is a noncollagenous adhesive protein routinely found at sites of dystrophic calcification and synthesized at high levels by macrophages in calcified aortic valves and atherosclerotic plaques. In the present study, we have characterized the calcification of bovine aortic smooth muscle cell (BASMC) cultures in vitro and have studied the effects of exogenous osteopontin on mineral deposition. Induction of calcification in BASMC cultures was alkaline phosphatase-dependent and was characterized by a multilayer cell morphology. Mineral deposition occurred in the basal matrix of multilayered areas as indicated by von Kossa staining, and transmission electron microscopy and electron diffraction identified the mineral as apatite. Ultrastructural analysis of the cultures showed the presence of extracellular matrix vesicles, calcifying collagen fibrils, and nodular-type calcifications similar to those found in calcified heart valves and atherosclerotic plaques. Purified osteopontin (0.05 to 5 microgram/mL) dose dependently inhibited calcification of BASMC cultures, whereas vitronectin and fibronectin had no effect. In contrast to the inhibitory mechanism of levamisole on mineral deposition, osteopontin did not inhibit alkaline phosphatase activity or reduce phosphorus levels in the culture medium. Addition of calcium to the cultures overcame the inhibitory effect of osteopontin on BASMC culture calcification and resulted in decreased levels of calcium in the culture medium and increased levels in the cell layer. Moreover, using high-resolution, colloidal-gold immunocytochemistry, osteopontin was found intimately associated with growing apatite crystals. These data indicate that the effect of osteopontin, although calcium-dependent, was not mediated by simple calcium chelation but most likely by direct interaction of osteopontin with crystal surfaces. These studies suggest that BASMCs can be used to model vascular calcification in vitro and that soluble osteopontin released near sites of vascular calcification may represent an adaptive mechanism aimed at preventing vascular calcification.
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PMID:Calcification of vascular smooth muscle cell cultures: inhibition by osteopontin. 993 48

About 50 mg of silver leaf (metallic silver) was given daily by mouth to 30 healthy volunteers for 20 days. A statistically significant hypophospholipidemic, hypotriglyceridemic, hypocholesterolemic and hypoglycemic effect was observed. This was accompanied by a less marked fall in total lipids and significant rise in HDL-cholesterol. In addition, a decrease in plasma enzymes - alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatine phosphokinase (CPK), gamma glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH) was noted. This was statistically significant for all enzymes except CPK. The safety of ingested silver foil is indicated by absence of pathology in urine and unaltered levels of protein and albumin in the plasma. These observations suggest that silver could be beneficial in conditions like diabetes mellitus, obesity and atherosclerosis.
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PMID:Effect of silver leaf on circulating lipids and cardiac and hepatic enzymes. 1023 75

Vascular calcification in advanced atherosclerosis is frequently associated with diabetes, and is a predictor of future cardiovascular events. To investigate the molecular mechanisms of vascular calcification, we examined whether advanced glycation endproducts (AGE) formed at an accelerated rate under diabetes induce the osteoblastic differentiation of pericytes, a mesenchymal progenitor. First, von Kossa staining demonstrated that AGE significantly increased the number of calcified nodules in a bovine pericyte culture. AGE were also found to induce calcium accumulation in the pericyte monolayer in time- and dose-dependent manners. Second, quantitative reverse transcription-polymerase chain reaction revealed that AGE increased the pericyte levels of mRNAs coding for alkaline phosphatase and osteopontin, the representative markers for early and late osteoblastic differentiation, respectively. Alkaline phosphatase activity was actually enhanced by AGE. The results suggest that AGE have the ability to induce the osteoblatic differentiation of pericytes, which would contribute to the development of vascular calcification in diabetes.
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PMID:Advanced glycation endproducts accelerate calcification in microvascular pericytes. 1032 91

The optimal surgical procedure for severe renal secondary hyperparathyroidism (sHPT) is still a point of controversy. Total parathyroidectomy (PTX) without auto-transplantation was abandoned for fear of an adynamic bone condition; however, in the case of autotransplantation recurrent sHPT is frequent and promotes atherosclerosis. We studied 11 hemodialysis patients (age 59+/-12 years) on dialysis for 18 (12-30) years in whom total PTX was performed due to severe sHPT (group I; intact PTH: 1,240+/-230 pg/ml), and 5 patients (age 55+/-10 years) without renal insufficiency who inadvertently received total PTX during thyroid surgery (group II). After total PTX (group I, 26+/-18 [9-59] months; group II, 252+/-188 [22 480] months) both groups showed no measurable intact PTH levels. Calcium homeostasis was maintained by oral substitution with calcium (group I, calcium dialysate of 2.0 mmol/l), vitamin D and calcitriol (serum parameters in groups I and II: calcium 2.4 and 2.2 mmol/l; phosphate 1.8 and 1.1 mmol/l; 25(OH)-vitamin D(3) 21 and 34 ng/ml; 1,25(OH)(2)-vitamin D(3) 32 and 41 pg/ml, respectively). In group I, after total PTX there was a rapid and sustained improvement in bone pain with markedly enhanced physical activity and endurance. High turnover osteopathy markedly improved as indicated by declining levels of native osteocalcin (90+/-17 vs. 26+/-18 ng/ml), bone alkaline phosphatase (74+/-12 vs. 12+/-6 ng/ml), and carboxyterminal cross-linked telopeptide of type-I collagen (65+/-16 vs. 40+/-21 ng/ml) but increasing levels of carboxyterminal propeptide of type-I procollagen (120+/-36 vs. 148+/-41 ng/ml). Recalcification of bone was excellent as demonstrated by X-ray and confirmed by bone histology. Itching extravascular calcific deposits and calcifications of blood vessel and cardiac valves immediately stopped after total PTX. Moreover, 6 sHPT patients suffered from severe atherosclerotic lesions such as thoracic aortic aneurysm (n = 3) or abdominal aortic aneurysm (n = 3) which showed size progression before but not after total PTX when annually controlled by ultrasonography. In group II, even long after total PTX, there was no clinical, radiological, histological or biochemical evidence for low turnover osteopathy. In conclusion, our data indicate that substitution with vitamin D(3) metabolites and calcium can prevent deleterious bone effects of hypoparathyroidism in hemodialysis patients and in patients with normal kidney function and may compensate for the missing PTH action. Over this, a better survival rate is expected as a consequence of the beneficial effect of total PTX on the progression of atherosclerotic lesions. We suggest reconsideration of total PTX without autotransplantation in dialysis patients with severe sHPT who are not eligible for renal transplantation.
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PMID:Long-term results of total parathyroidectomy without autotransplantation in patients with and without renal failure. 1043 1

This study was carried out to investigate the relationship between lipoprotein (a) levels and the development of atherosclerosis in chronic renal failure (CRF) patients with the possible role of the liver. Serum Lp (a) levels were measured in samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (transaminases (ALT and AST), alkaline phosphatase (ALP) and total bilirubin) investigations and serum cholesterol were carried out for all the subjects enrolled in this study. Serum Lp (a) concentration in CRF patients without LC was 87.25 +/- 6.17 mg/dl, which was significantly higher than all the investigated groups (P < 0.001). Lp (a) concentration in patients with both CRF and LC was 24.65 +/- 1.98 mg/dl, which was not significantly different from the controls, but was significantly higher than that in the subjects with LC only (P < 0.001) where the latter group had significantly low Lp (a) values (11.1 +/- 0.99) relative to all the other groups (P < 0.001). Lp (a) correlated positively with cholesterol in all groups except the LC subjects, but did not correlate with age, or renal function in both CRF groups.
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PMID:Serum lipoprotein (a) levels in chronic renal failure and liver cirrhosis patients. Relationship with atherosclerosis. 1068 47

Statins decrease the hepatic biosynthesis of cholesterol, and reduce the incidence of myocardial infarction in women who have already experienced a myocardial infarction. Statins also reduce the risk of atherosclerosis in diabetic patients, but it is unknown whether they influence the glucose tolerance. It has further been suggested that they may influence bone metabolism. Vitamin C is an antioxidant and it decreases serum cholesterol moderately. Antioxidants may also have other metabolic effects, but these are insufficiently studied. The aim of the present study was to investigate the metabolic effects of the cholesterol-lowering agent fluvastatin and the antioxidant vitamin C. Sixty-eight elderly, postmenopausal women with osteoporosis and mild hypercholesterolemia were randomly assigned to 12 weeks open treatment with either fluvastatin (40 mg daily) + 500 mg vitamin C (n = 45) or vitamin C only (n = 23). We measured biochemical markers of bone formation (serum osteocalcin and total alkaline phosphatase) and bone resorption (serum and urinary CTX), parameters related to diabetes and serum lipids and lipoproteins. Fluvastatin in combination with vitamin C had no effect on bone formation markers. We found a weak decrease in parameters of bone resorption, which was significant from baseline, but not different between the two groups. There were no significant effects on any of the other markers of either fluvastatin or vitamin C. The lipid-lowering effect of fluvastatin was confirmed with a decrease of 20% and 30% in serum total cholesterol and LDL-cholesterol, respectively. We conclude that fluvastatin given in clinically relevant doses has no influence on parameters of bone remodeling. Other statins remain to be investigated.
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PMID:The effect of fluvastatin on parameters of bone remodeling. 1144 86

Oxidative stress may regulate cellular function in multiple pathological conditions, including atherosclerosis. One feature of the atherosclerotic plaque is calcium mineral deposition, which appears to result from the differentiation of vascular osteoblastic cells, calcifying vascular cells (CVC). To determine the role of oxidative stress in regulating the activity of CVC, we treated these cells with hydrogen peroxide (H(2)O(2)) or xanthine/xanthine oxidase (XXO) and assessed their effects on intracellular oxidative stress, differentiation, and mineralization. These agents increased intracellular oxidative stress as determined by 2,7 dichlorofluorescein fluorescence, and enhanced osteoblastic differentiation of vascular cells, based on alkaline phosphatase activity and mineralization. In contrast, H(2)O(2) and XXO resulted in inhibition of differentiation markers in bone osteoblastic cells, MC3T3-E1, and marrow stromal cells, M2-10B4, while increasing oxidative stress. In addition, minimally oxidized low-density lipoprotein (MM-LDL), previously shown to enhance vascular cell and inhibit bone cell differentiation, also increased intracellular oxidative stress in the three cell types. These effects of XXO and MM-LDL were counteracted by the antioxidants Trolox and pyrrolidinedithiocarbamate. These results suggest that oxidative stress modulates differentiation of vascular and bone cells oppositely, which may explain the parallel buildup and loss of calcification, seen in vascular calcification and osteoporosis, respectively.
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PMID:Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. 1149 84

Elevated concentrations of asialylated LDL (asialo-LDL) have been reported in patients with coronary artery disease (CAD). This may stimulate lipid accumulation in arterial intima cells and promote atherosclerosis. To investigate asialo-LDL as a potential risk-factor for coronary atherogenesis, we developed an antibody-lectin sandwich assay to measure levels in serum from CAD patients and age-matched control subjects. LDL was captured with an anti-apolipoprotein (apo) B antibody and asialylated oligosaccharides measured using the biotinylated D-galactose (D-gal) binding lectin, Ricinus communis agglutinin 120 (RCA120), and a streptavidin-alkaline phosphatase conjugate. For the control and atherosclerotic subjects, median [interquartile range (IQR)] values for total concentrations of asialo-LDL were 240 mg,L (180-310 mg/L) and 220 mg/L (186-390 mg/L), respectively (P = 0.82). When expressed as a percentage of serum apo B-100, median (IQR) values were 18% (16-23%) and 19% (15-29%), respectively (P = 0.78). These results suggest asialo-LDL has little value as a risk factor for coronary atherosclerosis.
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PMID:Measurement of asialylated LDL in the blood of patients with coronary artery disease by antibody-lectin sandwich assay. 1158 28


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