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

The variation with age in distensibility and the dimensions of the abdominal aorta at the bifurcation have been measured in 43 fresh human cadavers. The age range was from birth to 69 years, both sexes being represented. Patients with vascular disease were excluded. Barium sulfate infused into the aorta through an iliac artery enabled the change in diameter to be measured from a roentgenogram with change in pressure. Incremental strain value could thus be calculated. Strain value increased from 0.02 at birth to a maximum at the end of the first decade of life and then decreased to less than 0.01 by the age of 70 years. Aortas in the age group of four to 11 years showed less stiffness with increasing pressure than at other ages. Variations of strain with age correlate with alterations in the ratio of aortic wall collagen to elastin in the young. An increase in the thickness of the wall and an atheroma, in response to prolonged hemodynamic stress, account for increased stiffness in the older age groups. Other age and disease factors may play a part, but further work is required in man to examine the role of relative wall thickness, elastic modulus and alteration in wall structure in determining the variation of aortic distensibility with age reported herein.
 ...
PMID:The effect of age on the distensibility of the abdominal aorta of man. 68 72

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.
 ...
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

The high-pressure systemic arterial network plays a major physiological role as it buffers the impact of the blood flow wave generated by the left ventricle and transforms it into a more continuous flow in the peripheral arterioles. In ageing processes unrelated to hypertensive or vascular disease the structural properties of the arterial network are significantly altered. The collagen, elastin and smooth muscle contents of the tunica media and the geometrical arrangement of arterial wall components are constantly modified according to the subject's age. These morphometric changes are responsible for changes in the mechanical properties of the arterial walls leading to rigidity. An increase in caliber of the arterial lumen has been found in all studies; it partially compensates for the effects of arterial wall rigidity on vascular compliance, thereby limiting the haemodynamic and functional changes that occur in blood circulation.
 ...
PMID:[Aging of the arterial system]. 140 73

One prediction of the protease-antiprotease hypothesis of chronic obstructive pulmonary disease (COPD) pathogenesis is the appearance of elastin-derived degradation products in the plasmas of affected patients that are due to the breakdown of alveolar interstitial elastin by an excess of elastolytic activity in the lung. We previously demonstrated a significant elevation of plasma elastin-derived peptides (EDP) in subjects with COPD in comparison with asymptomatic smokers with normal spirometry or normal nonsmokers. To better determine the selectivity of the assay for EDP as a marker of COPD, we measured plasma EDP levels in different patient populations. These included subjects with COPD, subjects with diseases that may involve accelerated elastolysis (pneumonia, atherosclerotic vascular disease, and inflammatory arthritis), subjects with diseases hypothesized to involve pulmonary inflammation without elastolysis (asthma and acute tracheobronchitis), asymptomatic smokers with normal spirometry, and healthy, nonsmoking subjects. Mean plasma EDP levels in subjects with COPD were elevated above those in all other subjects (p less than 0.01). The prospective analyses of specificity and sensitivity of plasma EDP levels as markers of COPD gave values of 91 and 65%, respectively. Utilizing receiver operating characteristic curve analysis to assess the diagnostic and screening performance of plasma EDP as a test for COPD (perfect test equals an area under the curve of 1.0), the area under the curve was 0.87, which compares favorably with many widely used clinical tests. These data demonstrate that the assay for plasma EDP is a quantitative, easily measured, and highly specific marker for subjects with COPD.
 ...
PMID:Specificity and sensitivity of the assay for elastin-derived peptides in chronic obstructive pulmonary disease. 846 8

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.
 ...
PMID:Investigational approaches to pulmonary hypertension. 181 89

We have identified several features which appear to play a key role in the pathogenesis of pulmonary vascular disease. Future work will involve exploring the regulation of elastase and elastin synthesis, control of smooth muscle proliferation and production of extracellular matrix. Application of cellular and molecular techniques in vascular research should ultimately lead to new and improved therapeutic approaches.
 ...
PMID:New developments in the pathogenesis of pulmonary hypertension in the newborn and child. 251 92

Auto-antibodies such as anti-elastin, anti-collagen, anti-nuclear and anti-arterial, circulating immune complexes, and cellular responses to collagen I and III are known to be present in Buerger's disease (EO). Deposits of IgG, C3 and C4 have also been found in the vascular lesions of endarteritis obliterans (EO) in young men. The purpose of this study was to correlate clinical evidence of vascular disease with the presence of the circulating immune complexes. Thirty-three patients suffering from Buerger's disease (EO), 20 patients suffering from atherosclerosis (AT) and 20 normal controls (Norm) were studied. All were male, heavy smokers, and age-matched. Five techniques were used: direct nephelometry, nephelometry with protamine, two polyethyleneglycol precipitation methods (PegIgG and PegC4), and an immuno-enzymatic C1q fixation test (C1qE). The results seem to confirm the presence of circulating immune complexes in peripheral arterial disease in young men who are heavy smokers, particularly those suffering from EO.
 ...
PMID:Circulating immune complexes in Buerger's disease. Endarteritis obliterans in young men. 280 5

We suggest that hypoxia-induced pulmonary hypertension in the newborn calf is an attractive model for studying the mechanisms underlying alterations in extracellular matrix accumulation which occur in pulmonary vascular disease. Our data support a model (Fig 7) in which the SMC, perhaps as a result of hypoxic and/or pressure-induced vessel wall injury, becomes phenotypically altered. This phenotypically altered SMC generates a factor, termed smooth muscle derived extracellular matrix factor (SMEF), and possibly other factors. SMEF, in turn, stimulates or induces elastin and collagen synthesis in fibroblasts and endothelial cells. SMEF, or an associated activity derived from phenotypically altered smooth muscle cells, also induces elastin receptor expression on the cell surface and affects the chemotactic responsiveness of vascular cells. Thus, the SMC may be able to affect both the secretory and responsive properties of cell types in the vascular wall. The SMC may be critical in the vascular remodeling in pulmonary hypertension. The possible autocrine or paracrine alteration of cellular phenotypes by smooth muscle-derived mediators provides an important new direction for future research into molecular and cellular mechanisms of connective tissue regulation in diseased vessels.
 ...
PMID:Vascular remodeling in neonatal pulmonary hypertension. Role of the smooth muscle cell. 334 91

Glycosaminoglycans (GAGs) have been implicated in the pathogenesis of sclerotic vascular disease. The localization of GAGs in the rat aorta was examined by two different ultrastructural cytochemical approaches. These procedures are believed to demonstrate 1) anionic sites, with fixatives that contain either toluidine blue or ruthenium red, both cationic dyes, and 2) polysaccharides, proteoglycans, and glycoproteins, with an osmium--ferrocyanide mixture that binds to vicinal diols. Both procedures stain a network of insoluble, 2--8-nm filaments that bridge collagen fibers, elastin, basement membranes, and plasma membranes. These structures resist digestion with chondroitinase ABC and appear to be identical to the filaments that have previously been demonstrated with ruthenium red. Focal 6--12-nm densities are present where filaments intersect. However, the large granules that are made visible with ruthenium red are not seen in toluidine blue or osmium--ferrocyanide preparations. A soluble and relatively amorphous component surrounds the tightly packed bundles of collagen in the media and is preserved and stained by toluidine blue and osmium--ferrocyanide mixtures.
 ...
PMID:Glycosaminoglycans in the rat aorta. Ultrastructural localization with toluidine blue O and osmium--ferrocyanide procedure. 617 40

Destruction (elastolysis) of the internal elastic lamina is frequently observed near early atherosclerotic plaques. Elastolysis and plaque formation are also found together in the temporal arteritis/polymyalgia rheumatica syndrome. Could it be that atherosclerosis and the syndrome are more closely akin than usually thought, with elastolysis acting as the pathogenetic link between them? A kinship of this nature is in accord with the growing recognition that elastin-related autoimmunity prevails in both these forms of vascular disease. A case can also be made out for the belief that the autoimmune reactions in internal vessels may be provoked by events in the integument where a slow but ultimately massive turnover of dermal and vascular elastic tissue takes place under the harmful influence of solar and other forms of actinic radiation.
 ...
PMID:Destruction of elastic tissue (elastolysis) as a link between atherosclerosis and the temporal arteritis/polymyalgia rheumatica syndrome. Observations on an actinic factor in vascular disease. 636 8


1 2 3 4 5 6 7 8 9 10 Next >>