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)

Impaired elastin fiber assembly is observed in the fetal ductus arteriosus (DA), associated with a reduced concentration of elastin binding protein (EBP), a 67-kDa galactolectin. It is also seen in cultured aortic (Ao) smooth muscle cells (SMC) following the release of the EBP by glycosaminoglycans rich in N-acetylgalactosamine, such as chondroitin sulfate (CS). In the DA, impaired elastin fiber assembly is observed in conjunction with intimal thickening associated with increased migration of SMC into the subendothelium, a feature we previously related to increased production of fibronectin. In this report, we determined whether SMC use the EBP to attach to an elastin substrate, whether shedding of the EBP promotes SMC migration through a three-dimensional network of pure elastic laminae prepared from sheep aorta, and whether the latter is associated with increased production of fibronectin. We observed reduced attachment to elastin-coated surfaces of DA SMC deficient in EBP compared to Ao SMC. Addition of CS but not heparan sulfate (a glycosaminoglycan which does not induce EBP shedding) decreased Ao SMC attachment to elastin, as did preincubation with VGVAPG elastin-derived peptides which saturate the EBP. The immunolocalization of cell surface EBP suggested that cells can quickly replace EBP released from their surfaces by CS treatment. The magnitude of CS-induced impaired attachment of SMC to elastin was dose dependent and could be further increased by the administration of cyclohexamide and sodium azide. Also, the reversibility of CS-induced detachment was prevented by monensin. This suggests that a process of new synthesis and intracellular transport of the EBP was necessary to replace the EBP molecules released from the cell surface by CS treatment. In the migration assay, both DA and Ao SMC attached to the top of an elastin membrane, but only DA SMC deficient in EBP migrated through the laminae. Addition of CS, which induced shedding of EBP, resulted in Ao SMC migration associated with increased synthesis of fibronectin. We postulate that CS-induced release of EBP from SMC surfaces causes cell detachment from elastin and an increase in fibronectin synthesis, processes which may be critical in promoting SMC migration associated with intimal thickening developmentally in the DA and perhaps also in vascular disease.
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PMID:Vascular smooth muscle cell detachment from elastin and migration through elastic laminae is promoted by chondroitin sulfate-induced "shedding" of the 67-kDa cell surface elastin binding protein. 133 80

Scleroderma fibrotic lesions demonstrate vascular disease, mononuclear cell infiltrates, and increased collagen. Fibroblasts in these lesions are activated to synthesize increased extracellular matrix substances, a phenotype that continues when these cells are removed and grown in tissue culture. Levels of messenger RNA for connective-tissue substances, measured directly in biopsies of scleroderma skin, show increased message for type I collagen, but not type III collagen or fibronectin. Increased procollagen type I in scleroderma skin occurs in the papillary dermis, perivascular areas, and deep interstitium, even in skin areas that are not yet fibrotic. Scleroderma fibroblasts express more intercellular adhesion molecule 1 on their surfaces than do normal cells, and this molecule is increased in endothelial cells, mononuclear cells, and fibroblasts. In vitro scleroderma fibroblasts adhere more frequently to extracellular matrix substances and retract collagen lattices to a greater extent. Peripheral blood lymphocytes from scleroderma patients produce excessive amounts of interleukin-2 when incubated with type I collagen, and circulating basophils release more histamine than do normal cells. There is evidence for activated eosinophils both in the dermis and pulmonary lesions in scleroderma, which may play a role in fibrosis. Transforming growth factor-beta is overexpressed by alveolar macrophages from patients with fibrotic pulmonary disease. Scleroderma fibroblasts, when exposed to transforming growth factor-beta, overexpress the alpha-type receptor for platelet-derived growth factor. Scleroderma sera more frequently contain measurable quantities of interleukin-4, interleukin-6, and interleukin-2. Interleukin-4 causes adult dermal fibroblasts to proliferate and to make interleukin-6. Interleukin-6 has been shown to stimulate fibroblast synthesis of collagen and glycosaminoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Connective tissue metabolism including cytokines in scleroderma. 145 83

The pathophysiology of peripheral circulatory disturbance in patients presenting with vibration syndrome was studied from the viewpoint of blood coagulation. Plasma levels of fibronectin (FN), vitronectin (VN), thrombin-antithrombin III complex (TAT), and alpha 2-plasmin inhibitor-plasmin complex (PIC) were measured in 23 subjects who showed no evidence of vibration-induced white finger [VWF(-) group] and in 24 patients who presented with VWF [VWF(+) group]. In the VWF(-) group, plasma FN concentrations were elevated but plasma TAT and PIC levels were within the normal ranges. In the VWF(+) group, plasma FN concentrations were normal but plasma TAT and PIC levels were significantly elevated. In both groups, plasma VN concentrations were similar to those in normal controls. For purposes of comparison, 32 patients presenting with diabetes mellitus were also studied. They were divided into 2 groups, 13 subjects who showed no evidence of angiopathy [complication(-) group] and 19 patients who presented with angiopathy [complication(+) group]. In the complication(+) group, plasma TAT and PIC concentrations were significantly elevated, as in the VWF(+) group. These results suggest that in vibration syndrome, vibration, cold stimulus, or other factors first injure the vascular endothelium, resulting in a rise in plasma FN, and that in the VWF(+) group, augmentation of coagulation and fibrinolysis induces a state of compensated disseminated intravascular coagulation (DIC).
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PMID:Activation of blood coagulation and fibrinolysis in vibration syndrome. 172 Jul 65

Pulmonary vascular disease (PVD) revolves around a series of switches in the smooth muscle cell (SMC) phenotype. Differentiation of SMC from precursor cells causes muscularization of normally non-muscular peripheral arteries; hypertrophy and hyperplasia of existing SMC and increased connective tissue protein synthesis cause thickening of the wall, and migration of SMC into the subendothelial space is the basis of intimal proliferation. To uncover the pathophysiologic mechanisms of these changes, we have used a variety of animal models and cell culture systems. From rats in which hypertensive PVD was induced by exposure to chronic hypoxia or following injection of the pyrrolizidine alkaloid, monocrotaline, we have identified increased pulmonary artery (PA) elastolytic activity which occurs early and which accompanies progressive rather than reversible PVD. Inhibition of elastolytic activity prevents or reduces PVD. We are cloning the gene for this new enzyme to study its regulation in PVD. To address the mechanism of SMC proliferation under conditions of high PA pressure and flow, we cultured endothelial cells on polyvinylchloride membranes and pulsated them at high pressure. This caused reduced synthesis of heparan sulfate. The resulting decrease binding of fibroblast growth factor would lessen its mitogenic effect and modulate SMC proliferation in response to other growth factors from platelets or serum. To study SMC migration, we cultured endothelial and SMC from the ductus arteriosus (a fetal vessel which spontaneously develops intimal proliferation in late gestation). The migratory SMC phenotype is a function of increased production of fibronectin governed by a translational control mechanism, and increased endothelial hyaluronan regulated by transforming growth factor beta. SMC migration is also related to impaired assembly of elastin, the result of a chondroitin sulfate-induced decrease in elastin binding proteins and the production of a novel 'defunct' 52 kD tropoelastin.
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PMID:Investigational approaches to pulmonary hypertension. 181 89

Altered permeability of vascular endothelium to macromolecules may play a role in vascular disease as well as vascular homeostasis. Because the shear stress of flowing blood on the vascular wall is known to influence many endothelial cell properties, an in vitro system to measure transendothelial permeability (Pe) to fluorescein isothiocyanate conjugated bovine serum albumin under defined physiological levels of steady laminar shear stress was developed. Bovine aortic endothelial cells grown on polycarbonate filters pretreated with gelatin and fibronectin constituted the model system. Onset of 1 dyn/cm2 shear stress resulted in a Pe rise from 5.1 +/- 1.3 x 10(-6) cm/s to 21.9 +/- 4.6 X 10(-6) cm/s at 60 min (n = 6); while 10 dyn/cm2 shear stress increased Pe from 4.8 +/- 1.5 X 10(-6) cm/s to 50.2 +/- 6.8 X 10(-6) cm/s at 30 min and 49.6 +/- 8.9 X 10(-6) cm/s at 60 (n = 9). Pe returned to preshear values within 120 and 60 min after removal of 1 and 10 dyn/cm2 shear stress, respectively. The data show that endothelial cell Pe in vitro is acutely sensitive to shear stress.
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PMID:Endothelial albumin permeability is shear dependent, time dependent, and reversible. 190 93

A monoclonal antibody (HK-249) that recognizes a glucosamine sulfate alpha 1----4 glucuronic acid-containing determinant in heparan sulfate (HS) chains of a basement membrane-derived heparan sulfate proteoglycan identified and immunolocalized HS specifically to the amyloid deposits in neuritic plaques (NPs), congophilic angiopathy (CA), as well as in neurofibrillary tangles (NFTs) and non-tangle-bearing neurons in the brains of Alzheimer's and Down's syndrome (DS) patients. Ultrastructural immunohistochemistry demonstrated that HS within neurons of Alzheimer's disease (AD) brain was localized to lipofuscin granules, an aging pigment previously shown also to contain beta-amyloid protein (BAP). Heparan sulfate also was localized to neurite-containing, nonfibrillar 'primitive' plaques that also demonstrated positive BAP immunoreactivity in both AD and DS brains. Antibodies to laminin, fibronectin, and a chondroitin sulfate proteoglycan failed to show positive immunostaining of the HS-containing sites described above. Analysis of DS patients at different ages revealed that HS accumulated within neurons of the hippocampus and amygdala as early as 1 day after birth. Young age-matched controls did not demonstrate similar positive HS immunoreactivity in neurons, whereas positive immunostaining for HS was observed in other regions thought to normally contain HS. The earliest deposition of BAP was first observed as 'amorphous' or 'diffuse' cortical deposits in DS brain in patients aged 18 and 24 years before the accumulation of fibrillar amyloid (observed in DS patients who are 35 years and older). These cortical deposits also contained positive HS immunoreactivity, implying that HS accumulation in conjunction with the BAP is an early event that ultimately may contribute to the early age-related accumulation (ie, as early as 35 years of age in DS) of NPs, NFTs, and/or CA. Furthermore the colocalization of HS and BAP in a number of specific locales in AD and DS brain indicates a possible interaction between these two macromolecules that may be important in lesion development in these two diseases.
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PMID:Early accumulation of heparan sulfate in neurons and in the beta-amyloid protein-containing lesions of Alzheimer's disease and Down's syndrome. 214 82

The peroxidase-immunoperoxidase immunocytochemical method was used on 27 saphenous vein coronary artery bypass grafts, which had been resected because of recurrent angina, to identify in situ cellular and humoral elements possibly associated with graft occlusion. Immunostaining was performed on paraffin wax embedded control saphenous vein and graft sections incubated directly with primary antibodies against von Willebrand antigen (vWFAg), fibronectin, fibrinogen, leucocyte common antigen (LCA), lysozyme, vimentin, desmin, platelet factor 4, and thrombospondin. Antigens were visualised by a chromogen providing an orange-red immunoprecipitate at the site of epitope localisation. The intraluminal, amorphous exudate present in most grafts was not composed simply of fibrin or fibrinogen, as previously thought, but was a multiprotein complex including wWFAg, fibronectin, thrombospondin and platelet factor 4. Along with macrophages, these components probably enter the graft after haemodynamic, physical, and chemical injury to, and disruption of, the endothelial cell. Progressive myointimal proliferation and fibrosis of these grafts may be local repetitive responses to macrophages and platelets, cells previously known to participate in vascular disease.
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PMID:Immunocytochemical features of obstructed saphenous vein coronary artery bypass grafts. 265 29

A study was initiated to determine whether alveolar macrophages from patients with collagen vascular diseases but free of pulmonary symptoms were spontaneously activated and whether they released various mediators related to the pathogenesis of pulmonary fibrosis. Alveolar macrophages obtained by bronchoalveolar lavage from 32 patients with proved collagen vascular disease but no evidence of lung disease were compared with those from 10 patients with collagen vascular disease with interstitial lung disease (CVD-ILD) and from 10 healthy controls. The total number of alveolar macrophages did not differ between patients with collagen vascular disease and controls but were substantially increased in the CVD-ILD group. Alveolar macrophages from 31 of the 32 patients with collagen vascular disease and from all 10 in the CVD-ILD group had at least one criterion of activation. Neutrophil chemotactic activity was detected in supernatants from alveolar macrophage culture in 23 of the 32 patients with collagen vascular disease and from nine of the 10 in the CVD-ILD group; fibronectin secretion by alveolar macrophages was increased in 12 of the 32 patients with collagen vascular disease and in nine of the 10 in the CVD-ILD group. Furthermore, alveolar macrophages from 20 of the 32 patients with collagen vascular disease and four of the 10 CVD-ILD patients spontaneously released increased amounts of superoxide anion. Thus alveolar macrophages were spontaneously activated in a high proportion of patients with collagen vascular disease.
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PMID:Activated alveolar macrophages in subclinical pulmonary inflammation in collagen vascular diseases. 283 61

To establish the relation between plasma fibronectin (PF) and vascular complications of diabetes mellitus, we studied 163 normotensive diabetic outpatients, of whom 53 were treated with insulin (15 type I, 38 type II) and 110 with sulfonylureas, and compared them to 34 control subjects. Diabetic patients were divided, according to their therapy, into four groups: with retinopathy (classified as background or proliferative) detected by fluorescein angiography (m), with macroangiopathy, assessed by clinical criteria (M), with both vessel complications (mM) and without vascular disease (N). PF was not related to glycosylated hemoglobin (HbA1) in each treatment group (r = 0.26; P = 0.051 in the insulin treated patients and r = 0.09; P = 0.356 in the group on oral drugs). PF levels were similar in M groups, either on insulin or sulfonylureas and in controls. Both m and mM subsets of patients were, conversely, characterized by significantly raised mean PF concentrations when compared to N subjects or controls, but proliferative retinopathy was not associated with a significant PF increase compared to background retinopathy. The differences of PF levels among m, mM and N groups remained significant after processing the data by means of stepwise discriminant analysis with age, duration of diabetes, body weight and HbA1 entering the model as covariates. We conclude that diabetic macroangiopathy is not associated with modifications of mean PF levels, which, on the contrary, appear increased only in diabetic patients with retinopathy, regardless of their therapy.
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PMID:Plasma fibronectin in diabetic retinopathy and macroangiopathy. 377 Feb 74

The microdistribution of type V collagen, fibronectin, and laminin on the luminal surface of perfusion-fixed normal rat aortic endothelium has been studied by an immunoelectron microscopic method using monospecific antibodies and a protein A-gold complex. Gold particles indicating the presence of these biologically active connective tissue proteins were localized in groups on and in the vicinity of the interendothelial border. They were also found on the small flaps of cell junctions as well as on certain cell projections and scattered on the cell surface. Correlative transmission electron-microscopic examinations proved the specificity of these localizations. The endothelial cells of the aorta differed markedly in the amount of scattered connective tissue proteins on their surface, suggesting that there are several types of aortic endothelial cells with distinct functional differences. The findings provide evidence that connective tissue proteins may contribute to the surface pattern of the normal endothelium, especially on cell borders. It is likely that these proteins influence functions such as the permeability and chemotactic activity of the endothelium pertinent to the development of vascular disease.
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PMID:Presence of connective tissue proteins on the endothelium of the rat aorta. 637 59


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