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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A boy with dermatomyositis which began at the age of one year and five months showed multiple migratory subcutaneous nodules, which have seldom been described. Histological and electron microscopic studies of muscles and subcutaneous nodules demonstrated the following interesting findings. 1. Light microscopy. The migratory subcutaneous nodules consisted of non-suppurative panniculitis and ischaemic adipo-necrosis as a sequel to vascular lesions. This finding suggests that the nodules may have arisen from the subcutaneous adipose tissue which had been severely damaged by systemic angiopathy. 2. Electron microscopy. Examination of the vessels in muscle and subcutaneous nodules showed tubular cytoplasmic inclusions with a diameter of approximately 250 A in the endoplasmic reticulum of vascular endothelial cells. These observations provide strong support for the concept that the fundamental pathologic process in childhood dermatomyositis is of a vascular nature, and the primary lesion is in the walls of the intramuscular blood vessels.
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PMID:Tubular cytoplasmic inclusions in a case of childhood dermatomyositis with migratory subcutaneous nodules. 89 72

Ultrastructural studies of serial sections of the vessels with amyloid deposits in the brain cortex of patients with Alzheimer's disease showed that cells in the position of pericytes--perivascular cells--and perivascular microglial cells are producers of amyloid fibrils in the vascular wall. Three types of changes from normal are distinguishable in the vessel wall: (1) semicircular or circular thickening of vascular wall containing a large amount of amorphous material and various number of amyloid fibrils, (2) tuberous amyloid deposits containing both amorphous material and amyloid fibrils, some of the fibrils being arranged in strata and others arranged radially, and (3) amyloid star composed of a predominantly radial arrangement of bundles of amyloid fibrils and a less prominent amorphous component. A mixture of amorphous material and amyloid fibrils is present in cell membrane invaginations of perivascular cells, and occasionally perivascular microglial cells. Bundles of amyloid fibrils are found in altered cisternae of the endoplasmic reticulum and in the channels confluent with the infoldings of the plasma membrane of perivascular microglial cells. The amyloid deposition in the wall of the vessel causes degeneration of endothelial cells and the reduction of, and in some vessels obliteration of, the vessel lumen. In areas affected by amyloid angiopathy, extensive degeneration both of the neuropil and of neurons was observed. These changes were accompanied by astrogliosis. This study demonstrates similarities in amyloid formation in amyloid angiopathy and in beta-amyloid plaques in the neuropil and suggests that cells of the mononuclear phagocyte system of the brain (perivascular cells and perivascular microglia) are engaged in amyloid fibril formation.
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PMID:Ultrastructural studies of the cells forming amyloid in the cortical vessel wall in Alzheimer's disease. 138 56

PDMs tend to be large and the size is generally in proportion to fetal size. Infarcts are both more numerous and more common in PDMs than in normal placentas. These reflect the in utero hypoxia found in IDMs. Placental infarcts are increased not only in cases of severe DM (classes D, F-R) but also mild and early DM (class A). We infer from this that maternal vascular disease may be present functionally long before pathologic changes can be detected by direct examination of vessels. More subtle evidence of hypoxia in PDMs, such as an increased number of syncytial knots, has been suggested by qualitative data but has not been confirmed by morphometric analysis. Other qualitative observations in PDMs include thickened basement membranes, flattened microvilli on trophoblasts, ectasia of capillaries and villous stromal edema; changes in intracellular organelles and structures include enlarged mitochondria, increased pinocytotic vesicles, and dilated profiles of endoplasmic reticulum. Quantitative morphometric analysis shows no differences between normal placentas and PDMs with regard to these changes. The transport and secretory functions of the placenta, especially important in pregnancy complicated by DM, are not addressed here. As our understanding of placental physiology enlarges, it will be useful to relate each function with its structural counterpart. Perhaps this review will in part provide rational data from which to proceed with the task.
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PMID:Placentas in pregnancies complicated by maternal diabetes. 639 Jun 23

The smooth muscle cell is the sole cell type normally found in the media of mammalian arteries. In the adult, it is a terminally differentiated cell that expresses cytoskeletal marker proteins like smooth muscle alpha-actin and smooth muscle myosin heavy chains, and contracts in response to chemical and mechanical stimuli. However, it is able to revert to a proliferative and secretory active state equivalent to that seen during vasculogenesis in the fetus, and this is a prerequisite for the involvement of the smooth muscle cell in the formation of atherosclerotic and restenotic lesions. A similar transition from a contractile to a synthetic phenotype occurs when smooth muscle cells are established in culture. Accordingly, an in vitro system has been used extensively to study the regulation of differentiated properties and proliferation of these cells. During the first few days after seeding, the cells are reorganized structurally with a loss of myofilaments and formation of a widespread endoplasmic reticulum and a prominent Golgi complex. In parallel, they lose their contractility and instead become competent to divide in response to a large variety of mitogens, including platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF). After entering the cell cycle, they start to produce these and other mitogens on their own, and continue to replicate in the absence of exogenous stimuli for a restricted number of generations. Furthermore, they start to secrete extracellular matrix components such as collagen, elastin, and proteoglycans. The mechanisms that control this change in morphology and function of the smooth muscle cells are still poorly understood. Adhesive proteins such as fibronectin and laminin apparently have an important role in determining the basic phenotypic state of the cells and exert their effects via integrin receptors. The proliferative and secretory activities of the cells are influenced by a multitude of growth factors, cytokines, and other molecules. Although much work remains before an integrated view of this regulatory machinery can be achieved, there is no doubt that the cell culture technique has contributed substantially to our knowledge of smooth muscle differentiation and growth. At the same time, it has been crucial in exploring the role of these cells in vascular disease and developing new therapeutic strategies to cope with major causes of human death and disability.
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PMID:Differentiated properties and proliferation of arterial smooth muscle cells in culture. 884 55

Smooth muscle cells build up the media of mammalian arteries and constitute one of the principal cell types in atherosclerotic and restenotic lesions. Accordingly, they show a high degree of plasticity and are able to shift from a differentiated, contractile phenotype to a less differentiated, synthetic phenotype, and then back again. This modulation occurs as a response to vascular injury and includes a prominent structural reorganization with loss of myofilaments and formation of an extensive endoplasmic reticulum and a large Golgi complex. At the same time, the expression of cytoskeletal proteins and other gene products is altered. As a result, the cells lose their contractility and become able to migrate from the media to the intima, proliferate, and secrete extracellular matrix components, thereby contributing to the formation of intimal thickenings. The mechanisms behind this change in morphology and function of the smooth muscle cells are still incompletely understood. A crucial role has been ascribed to basement membrane proteins such as laminin and collagen type IV and adhesive proteins such as fibronectin. A significant role is also played by mitogenic proteins such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF). An improved knowledge of the regulation of smooth muscle differentiated properties represents an important part in the search for new methods of prevention and treatment of vascular disease.
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PMID:Phenotypic modulation of smooth muscle cells during formation of neointimal thickenings following vascular injury. 969 Jan 43

Recent epidemiological studies have shown that vascular risk factors may be involved in Alzheimer's disease (AD) as well as dementia in general. To investigate the relation between a vascular disorder and AD pathology, current criteria are defective because most depend on exclusion of a cerebrovascular disorder. Epidemiological studies have indicated the possibilities that arteriosclerosis, abnormal blood pressure, diabetes mellitus and smoking may be related to the pathogenesis of AD. As for the mechanism that vascular disorders influence AD, it is presumed that amyloid deposition may be caused by a vascular disorder. Alternatively, a vascular event may cause progression of subclinical AD to a clinical stage. Insulin resistance and apolipoprotein E may also be involved in these mechanisms. Our studies show that ischemia-induced the Alzheimer-associated gene presenilin 1 (PS1) and endoplasmic reticulum-stress, generated from a vascular disorder, may unmask clinical AD symptoms caused by presenilin mutation, suggesting that a vascular factor might be involved in the onset of familial AD.
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PMID:Are cerebrovascular factors involved in Alzheimer's disease? 1086 6

Hyperhomocysteinemia, a risk factor for vascular disease, injures endothelial cells through undefined mechanisms. We previously identified several homocysteine-responsive genes in cultured human vascular endothelial cells, including the endoplasmic reticulum (ER)-resident molecular chaperone GRP78/BiP. Here, we demonstrate that homocysteine induces the ER stress response and leads to the expression of a novel protein, Herp, containing a ubiquitin-like domain at the N terminus. mRNA expression of Herp was strongly up-regulated by inducers of ER stress, including mercaptoethanol, tunicamycin, A23187, and thapsigargin. The ER stress-dependent induction of Herp was also observed at the protein level. Immunochemical analyses using Herp-specific antibodies indicated that Herp is a 54-kDa, membrane-associated ER protein. Herp is the first integral membrane protein regulated by the ER stress response pathway. Both the N and C termini face the cytoplasmic side of the ER; this membrane topology makes it unlikely that Herp acts as a molecular chaperone for proteins in the ER, in contrast to GRP78 and other ER stress-responsive proteins. Herp may, therefore, play an unknown role in the cellular survival response to stress.
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PMID:Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress. 1092 62

L-3-hydroxyacyl-coenzyme A dehydrogenase type II (HADH) was described as an endoplasmic reticulum amyloid beta-peptide-binding protein (ERAB), which enhances Abeta toxicity, and accumulates in neurons in Alzheimer's disease (AD). Hence, HADH/ERAB was suggested to mediate the amyloid-induced neurodegeneration. We estimated the in vivo interactions of HADH and Abeta in an immunocytochemical study of ten Alzheimer's disease and seven normal brains using five monoclonal HADH-specific antibodies. We found no HADH in amyloid plaques or vascular amyloid. The neuronal expression of HADH was not correlated with the severity of amyloid load in neuropil. HADH was expressed in vascular smooth muscle cells in young and old controls and in amyloid-free blood vessels in AD cases, but little or no HADH was in smooth muscle cells in arteries with amyloid deposits. The putative intracellular interaction between HADH and Abeta in amyloid-producing cells was further studied in vascular smooth muscle cells isolated from brain blood vessels with amyloid-beta angiopathy - the cells that were shown previously to accumulate Abeta intracellularly ['Research advances in Alzheimer's disease and related disorders' (1995) 747; Brain Res. 676 (1995) 225; Neurosci. Lett. 183 (1995) 120]. HADH had a mitochondrial localization and did not co-localize with an endoplasmic reticulum marker. Cells that accumulated Abeta were those with low expression of HADH and the proteins did not co-localize. Explanation of the association between low levels of HADH and deposition of Abeta by brain smooth muscle cells requires further studies.
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PMID:Deposition of Alzheimer's vascular amyloid-beta is associated with decreased expression of brain L-3-hydroxyacyl-coenzyme A dehydrogenase (ERAB). 1143 Aug 84

Caveolin-1 traffics cholesterol between the endoplasmic reticulum and cell surface caveolae in a non-vesicle chaperone complex which contains heat shock protein 56, cyclophilin 40, and cyclophilin A. Recent studies demonstrate that endothelial nitric oxide synthase (eNOS), caveolin, hetero-trimeric G-protein coupled receptors, and a calcium channel form an activation complex that is associated with cholesterol-rich caveolae. Oxidized LDL depletes caveolae of cholesterol and prevents agonist stimulation of eNOS by disrupting the activation complex. HDL antagonizes the effects of oxLDL by donating cholesterol to caveolae, thereby preserving the structure and function of caveolae. These findings and others provide a possible mechanistic basis for some of the molecular changes observed in vascular disease.
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PMID:Influence of caveolin, cholesterol, and lipoproteins on nitric oxide synthase: implications for vascular disease. 1167 56

Endothelial cell injury underlies an increased occurrence of thromboembolic vascular disease in hereditary hyperhomocysteinemia. We have previously shown that homocysteine causes activation of c-Jun NH(2)-terminal kinase (JNK) and activating transcription factor 3/liver regenerating factor 1 (ATF3/LRF1) and induces apoptosis in human umbilical vein endothelial cells (HUVECs). In this study, the activation of JNK and ATF3 in HUVECs was mediated by the endoplasmic reticulum (ER) resident transmembrane kinase IRE1alpha and beta, which sense and transduce signal of the accumulationj of unfolded proteins in the ER. Moreover, dominant negative mutants of tumor necrosis factor receptor-associated factor 2 and mitogen-activated kinase kinase 4 and 7, as well as antisense ATF3 cDNA, inhibited cell death by homocysteine. These results indicate that the activation of JNK and ATF3 through the ER stress of homocysteine plays a role in the homocysteine-induced cell death. The JNK-ATF3 pathway may be implicated in endothelial cell injury associated with hereditary hyperhomocysteinemia.
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PMID:Activation of JNK and transcriptional repressor ATF3/LRF1 through the IRE1/TRAF2 pathway is implicated in human vascular endothelial cell death by homocysteine. 1172 7


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