Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphologic and histochemical characteristics of selected portions of normal arteries from two species known to differ in susceptibility to vascular disease were examined. Arteries were classified as predominantly elastic, muscular or complex. Species differences in the structural organization of the abdominal aortic segment were observed. Arterial mucopoly-saccharides were stained more intensely in the tunica intima and media of chicken vessels than within those of the rat, and tended to be most concentrated in proximity of the internal elastic membrane. Histochemical procedures for the demonstration of enzymatic activity revealed inter-and intraspecies variations in vascular metabolism. Pronounced differences in reaction intensity for hydroxybutyrate dehydrogenase and malic enzyme, affecting chicken and rat coronary arteries, were noted. In contrast, theses vessels displayed only minimal activity for acid phosphatase. Marked endothelial deposition of alkaline phosphatase reaction products in the arteries of the chicken was demonstrated, while this enzyme's activity in the vessels of the rat was restricted to the tunica adventitia. The implications of these structural and histochemical factors with regard to vascular susceptibility to disease were discussed.
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PMID:Comparative morphological and histochemical aspects of selected arteries in the chicken and rat. 13 17

Changes in microvascular dimensions occurring with normal aging and Alzheimer's dementia were measured in thick sections of postmortem human visual cortex stained for alkaline phosphatase. Capillary density was decreased to the same degree in both normal aged and demented aged subjects. The fields selected for analysis in both groups included all cortical laminae and, where possible, amyloid-cored neuritic plaques. The mean density of such plaques in these selected fields was slightly but not significantly higher in the demented group. In both groups plaques were more plentiful in visual laminae with the highest capillary densities (II-IV), but plaques and vessels were closer to each other in the normal aged than in the demented. Plaque distributions differed; in the normal aged, plaques concentrated in lamina IV; in the demented they were more evenly spread throughout the laminae. Plaque cores were larger in the demented. Amyloid angiopathy was more common and more extensive in the demented group; amyloid-cored plaques were not closely associated with affected vessels. Plaque distributions in Alzheimer subjects with and without amyloid angiopathy differed; plaque density was greatest in those without angiopathy. Alzheimer's dementia was not associated with any decline in microvascularity. Plaque concentration in well vascularized laminae suggests a pathogenetic role for some blood-borne agent. Differences in plaque distributions imply that the role or the agent differs in normal and demented aging, or perhaps between cases with and without amyloid angiopathy.
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PMID:Neuritic plaques and vessels of visual cortex in aging and Alzheimer's dementia. 238 95

Calcification is a common feature of advanced atherosclerotic lesions and is being reemphasized as a clinically significant element of vascular disease. However, the scarcity of in vitro models of vascular calcification preclude studying its molecular and cellular mechanism. In the present study, we describe an in vitro calcification in which diffuse calcification can be induced by culturing bovine vascular smooth muscle cells (BVSMC) in the presence of beta-glycerophosphate, ascorbic acid, and insulin in a manner analogous to in vitro mineralization by osteoblasts. Calcification was confirmed by von Kossa staining and 45Ca accumulation. Factor analysis revealed that beta-glycerophosphate is the most important factor for this calcification process, suggesting that alkaline phosphatase (ALP) may be involved. As predicted, high levels of ALP expression were detected by ALP assay and Northern blot analysis. Functional significance of ALP was confirmed by demonstrating that levamisole, a specific inhibitor of ALP, inhibited BVSMC calcification in a dose-dependent manner. Bisphosphonates such as etidronate and pamidronate potently inhibited BVSMC calcification, suggesting that hydroxyapatite formation may be involved. Importantly, expression of osteopontin mRNA was dramatically increased in calcified BVSMC compared with uncalcified control cells. These data suggest that beta-glycerophosphate can induce diffuse calcification by an ALP-dependent mechanism and that this in vitro calcification system is useful for analyzing the molecular and cellular mechanisms of vascular calcification.
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PMID:Beta-glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. 758 82

The role of the cAMP signaling pathway in vascular calcification was investigated using calcifying vascular cells (CVC) derived from primary aortic medial cell cultures. We previously showed that CVC have fibroblastic morphology and express several osteoblastic differentiation markers. After confluency, they aggregate into cellular condensations, which later mature into nodules where mineralization is localized. Here, we investigated the effects of cAMP on CVC differentiation because it plays a role in both osteoblastic differentiation and vascular disease. Dibutyryl-cAMP or forskolin treatment of CVC for 3 days induced osteoblast-like "cuboidal" morphology, inhibited proliferation, and enhanced alkaline phosphatase activity, all early markers of osteoblastic differentiation. Isobutylmethylxanthine and cholera toxin had the same effects. Treatment of CVC with pertussis toxin, however, did not induce the morphological change or increase alkaline phosphatase activity, although it inhibited CVC proliferation to a similar extent. cAMP also increased type I procollagen production and gene expression of matrix gamma-carboxyglutamic acid protein, recently shown to play a role in in vivo vascular calcification. cAMP inhibited the expression of osteopontin but did not affect the expression of osteocalcin and core binding factor. Prolonged cAMP treatment enhanced matrix calcium-mineral incorporation but inhibited the condensations resulting in diffuse mineralization throughout the monolayer of cells. Treatment of CVC with a protein kinase A-specific inhibitor, KT5720, inhibited alkaline phosphatase activity and mineralization during spontaneous CVC differentiation. These results suggest that the cAMP pathway promotes in vitro vascular calcification by enhancing osteoblast-like differentiation of CVC.
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PMID:cAMP stimulates osteoblast-like differentiation of calcifying vascular cells. Potential signaling pathway for vascular calcification. 951 56

Tissue nonspecific alkaline phosphatase (AP) plays a well-known role in bone mineralization. This role was first suggested by a human AP deficiency disease, hypophosphatasia. Further studies with AP gene knockout mice have also suggested a role for AP in mineralization. However, AP is also expressed in other human tissues besides bone and cartilage, and this raises a question as to whether AP may also play a role in pathological mineralization such as dystrophic and vascular calcification. In vitro studies carried out in our laboratory indicate that a variety of cell types stably expressing membrane-bound AP can affect extracellular mineralization regardless of the tissue from which the cell lines originated (e.g. fibroblasts, vascular endothelial cells, or renal epithelial cells). This AP-mediated extracellular mineralization is both substrate/dependent and culture environment/dependent and may be consistent with a putative role for AP in pathological mineralization in tissues other than bone and cartilage. In this regard, it is interesting to note that high levels of AP are observed in vascular endothelia of small arterioles in brain and heart. It is probable that expression of AP in small arterioles of brain and heart may also contribute to the vascular hardening and calcification observed in humans. This in turn could be related to vascular aging, vascular disease, and the resultant weakening of and/or rupture of vessel walls.
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PMID:New face of an old enzyme: alkaline phosphatase may contribute to human tissue aging by inducing tissue hardening and calcification. 970 Mar 94

This study sought to identify any benefit of routine liver function tests (LFTs) in chronically ill, geriatric patients and to assess which patients require evaluation for abnormal LFT levels. A retrospective chart review was carried out on 268 consecutive patients (M:F = 1.2, mean age 77 years, range 61-98 years) presenting for acute care from a long-term care facility. All were without jaundice, right upper quadrant pain, pruritus, bruising, or signs of chronic liver disease. The degree of LFT abnormality (aspartate aminotransferase, alanine aminotransferase, total bilirubin, or alkaline phosphatase) during admission was compared to the clinical diagnosis at the time of discharge. The most common diagnoses were pneumonia, urinary tract infection, and peripheral or coronary disease in 186 (60%). Thirty-seven patients (14%) had elevated LFT levels on admission. The levels normalized within 2 days in 26 of these patients, 25 of whom had a history of vascular disease (96%). Of the 11 remaining patients, 4 had coexistent vascular disease (36%), and 5 had LFT levels twice normal (none with vascular disease) and underwent abdominal ultrasound. One patient had a common bile duct stone successfully extracted. Enzyme abnormalities were due to hepatitis B or medication use in 10 of 11 patients. No patient had liver biopsy. All but one of the 268 patients were discharged without further evaluation. Over one year of follow up, no patient returned for a liver-related problem. Based on these findings, only those patients with LFT levels that are twice normal and which do not normalize within 2 days warrant further evaluation. Transient LFT abnormalities may be due to decreased liver perfusion.
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PMID:Outcomes of routine testing of liver enzymes in institutionalized geriatric patients. 1016 61

Leptin, the product of the ob gene, regulates food intake, energy expenditure, and other physiological functions of the peripheral tissues. Leptin receptors have been identified in the hypothalamus and in extrahypothalamic tissues. Increased circulating leptin levels have been correlated with cardiovascular disease, obesity, aging, infection with bacterial lipopolysaccharide, and high-fat diets. All these conditions have also been correlated with increased vascular calcification, a hallmark of atherosclerotic and age-related vascular disease. In addition, the differentiation of marrow osteoprogenitor cells is regulated by leptin. Thus, we hypothesized that leptin may regulate the calcification of vascular cells. In this report, we tested the effects of leptin on a previously characterized subpopulation of vascular cells that undergo osteoblastic differentiation and calcification in vitro. When treated with leptin, these calcifying vascular cells had a significant 5- to 10-fold increase in alkaline phosphatase activity, a marker of osteogenic differentiation of osteoblastic cells. Prolonged treatment with leptin enhanced the calcification of these cells, further supporting the pro-osteogenic differentiation effects of leptin. Furthermore, the presence of the leptin receptor on calcifying vascular cells was demonstrated using reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blot analysis. We also identified the presence of leptin receptor in the mouse artery wall, localized to subpopulations of medial and adventitial cells, and the expression of leptin by artery wall cells and atherosclerotic lesions in mice. Taken together, these results suggest that leptin regulates the osteoblastic differentiation and calcification of vascular cells and that the artery wall may be an important peripheral tissue target of leptin action.
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PMID:Leptin enhances the calcification of vascular cells: artery wall as a target of leptin. 1134 6

Diabetes is associated with an increased prevalence of atherosclerotic vascular disease and cardiovascular mortality. In diabetic patients, medial calcification appears to be a strong independent predictor of cardiovascular mortality, it occurs particularly in those with neuropathy. Recent evidence suggests that medial calcification in diabetes is an active, cell-mediated process, similar to that observed in patients with end-stage renal disease (ESRD), in which vascular smooth muscle cells (VSMCs) express a number of bone matrix proteins that act to either facilitate or regulate the calcification process. Several bone-associated proteins (e.g., osteopontin, bone sialoprotein, alkaline phosphatase, type 1 collagen, osteocalcin) have been demonstrated in histologic sections of vessels obtained from patients with diabetes or ESRD. In in vitro experiments, high glucose induced cell proliferation and expression of osteopontin in cultured VSMCs. Hypoxia had additive effects of hyperglycemia on VSMCs. In addition, uremic serum upregulates osteoblast transcription factor Cbfa 1 and osteopontin expression in cultured VSMCs. The pathogenesis of vascular calcification in diabetes is not completely understood, although high glucose and other potential factors may play an important role by transforming VSMCs into osteoblast-like cells. Further understanding of the mechanism by which diabetes induces this complication is needed to design effective therapeutic strategies to intervene with this process.
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PMID:Arterial calcification in diabetes. 1264 43

Insufficient growth and rarefaction of capillaries, followed by endothelial dysfunction may represent one of the most critical mechanisms involved in heart damage. In this study we examined histochemical and ultrastructural changes in myocardial capillary endothelium in two models of heart failure streptozotocin-induced diabetes mellitus (STZ) and NO-deficient hypertension in male Wistar rats. Diabetes was induced by a single i.v. dose of STZ (45 mg/kg) and chronic 9-week stage was analysed. To induce NO-deficient hypertension, animals were treated with inhibitor of NO synthase L-nitroarginine methylester (L-NAME) (40 mg/kg) for 4 weeks. Left ventricular tissue was processed for enzyme catalytic histochemistry of capillary alkaline phosphatase (AlPh), dipeptidyl peptidase IV (DPP IV), and endothelial NO synthase/NADPH-diaphorase (NOS) and for ultrastructural analysis. In diabetic and hypertensive rats, lower/absent AlPh and DPP IV activities were found in focal micro-areas. NOS activity was significantly reduced and persisted only locally. Quantitative evaluation demonstrated reduction of reaction product intensity of AlPh, DPP and NOS by 49.50%, 74.36%, 20.05% in diabetic and 62.93%, 82.71%, 37.65% in hypertensive rats. Subcellular alterations of endothelial cells were found in heart of both groups suggesting injury of capillary function as well as compensatory processes. Endothelial injury was more significant in diabetic animals, in contrast the adaptation was more evident in hypertensive ones. CONCLUDING: both STZ-induced diabetes- and NO-deficient hypertension-related cardiomyopathy were accompanied by similar features of structural remodelling of cardiac capillary network manifested as angiogenesis and angiopathy. The latter was however, predominant and may accelerate disappearance of capillary endothelium contributing to myocardial dysfunction.
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PMID:Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension. 1604 16

A 26-year-old man was admitted to the department of surgery of our hospital with a complaint of intermittent left leg pain for the past two weeks. Ultrasonography revealed reduced blood flow to the tibial artery, which suggested a vascular disease like arteriosclerosis obliterans. Enhanced computed tomography (CT) revealed a huge abdominal tumor and a 3-dimensional CT scan showed a feeding artery from the left renal artery to the huge tumor. Findings of routine blood and urine examinations were elevated levels of lactate dehydrogenase, alkaline phosphatase, and C-reactive protein. Surgical exploration revealed a giant tumor with clouded ascites in the abdominal cavity containing class V cells revealed by cytological examination. The tumor was easily resected. Its vascular pedicle was thick and hypertrophied. Thus, it could be traced to the origin of left gonadal artery. At this time, the surgeon incidentally noticed the absence of left testis in the patient's scrotum. The resected specimen was 25 x 18 x 12 cm in size, and it weighed 3000 gm. The histological finding was pure seminoma invaded to peritoneum. His leg pain was relieved after the tumor resection.
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PMID:[Giant seminoma in abdominal retention of the testis manifested with unilateral leg pain: a case report]. 1611 13


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