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)

Patients with insulin-dependent diabetes mellitus (IDDM) are well known to be at high risk of vascular disease, and dysfunction of vascular endothelium is considered as an early step in the development of diabetic complications. Because of the involvement of autoimmunity in the pathogenesis of IDDM, our aim was to assess, in 45 IDDM patients without clinically evident vascular complications, whether early signs of endothelial cell dysfunction were correlated to alterations of the immune system. IDDM patients were characterized by significantly increased serum levels of C-reactive protein, of polymorphonuclear cells-derived elastase, of endothelin-1 (ET-1) and of thrombomodulin, while plasma concentrations of fibronectin (FNT) were significantly decreased, with a statistically significant inverse correlation between ET-1 and FNT values. The presence of circulating immune complexes (CIC) was investigated in 36 out of our 45 IDDM patients, and values above the cut-off were found in 17 (47.2%) of them. One-third of all patients showed values above the cut-off for IgG-aCL. In IDDM patients, at variance from the control group, the levels of ET-1 were directly correlated to those of von Willebrand factor, of anticardiolipin beta(2)-GPI and of CIC, with an inverse correlation with plasma FNT. An association between antiphospholipid antibodies and endothelial dysfunction and/or activation is therefore suggested, pointing to a synergism, in the early phases of IDDM vascular disease, between generation of autoantibodies and endothelial activation.
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PMID:Autoantibodies and endothelial dysfunction in well-controlled, uncomplicated insulin-dependent diabetes mellitus patients. 1150 Jan 97

Information is rapidly emerging regarding the important role of the arterial vasa vasorum in a variety of systemic vascular diseases. In addition, increasing evidence suggests that progenitor cells of bone marrow (BM) origin may contribute to postnatal neovascularization and/or vascular wall thickening that is characteristic in some forms of systemic vascular disease. Little is known regarding postnatal vasa formation and the role of BM-derived progenitor cells in the setting of pulmonary hypertension (PH). We sought to determine the effects of chronic hypoxia on the density of vasa vasorum in the pulmonary artery and to evaluate if BM-derived progenitor cells contribute to the increased vessel wall mass in a bovine model of hypoxia-induced PH. Quantitative morphometric analyses of lung tissue from normoxic and hypoxic calves revealed that hypoxia results in a dramatic expansion of the pulmonary artery adventitial vasa vasorum. Flow cytometric analysis demonstrated that cells expressing the transmembrane tyrosine kinase receptor for stem cell factor, c-kit, are mobilized from the BM in the circulation in response to hypoxia. Immunohistochemistry revealed an increase in the expression of c-kit+ cells together with vascular endothelial growth factor, fibronectin, and thrombin in the hypoxia-induced remodeled pulmonary artery vessel wall. Circulating mononuclear cells isolated from neonatal calves exposed to hypoxia were found to differentiate into endothelial and smooth muscle cell phenotypes depending on culture conditions. From these observations, we suggest that the vasa vasorum and circulating progenitor cells could be involved in vessel wall thickening in the setting of hypoxia-induced PH.
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PMID:Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells. 1275 86

Homocysteine affects the migration and differentiation of neural crest cells in vitro and can result in neural tube defects in vivo. Furthermore, homocysteine has been described as an important determinant in vascular disease in human adults. However, little is known about the effects of homocysteine on the development of embryonic vessels. In this study, we injected homocysteine (30 micromol/L) into the neural tube lumen of chick embryos at the time point of neural crest cell emigration, and analyzed the effects on the neural crest-derived pharyngeal arch arteries, like the brachiocephalic arteries, and the mesoderm-derived arteries, such as the dorsal aorta. By stage HH35, we observed detachment of the endothelium, decreased expression of the extracellular matrix proteins fibrillin-2, and fibronectin in the pharyngeal arch arteries, whereas the dorsal aorta was identical in homocysteine-neural tube-injected and control embryos. No effect of homocysteine on endothelin-1 mRNA expression was observed. By stage HH40, the brachiocephalic arteries of homocysteine-neural tube-injected embryos displayed a decreased lumen diameter, an increased intima- and media-thickness, and an increased number of actin layers compared with the brachiocephalic arteries in control embryos. We propose that homocysteine affects the neural crest-derived smooth muscle cells and their extracellular matrix proteins in the pharyngeal arch arteries, resulting in an abnormal smooth muscle to endothelial cell interaction, leading to endothelial cell detachment. We suggest that, as in adult life, increased homocysteine concentrations lead to vascular damage in the embryo. This prenatal damage might increase the susceptibility to develop vessel pathology later in life.
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PMID:Homocysteine induces endothelial cell detachment and vessel wall thickening during chick embryonic development. 1469 14

Recruitment and activation of polymorphonuclear neutrophils (PMNs) reflects a primary immunological response to invading pathogens and has also emerged as a hallmark of vascular inflammation. One of the principal enzymes released upon PMN activation is myeloperoxidase (MPO), a heme protein that not only generates cytotoxic oxidants but also impacts deleteriously on nitric oxide-dependent signaling cascades within the vasculature. Because MPO also associates with the membrane of PMN, we evaluated whether MPO could also function as an autocrine modulator of PMN activation. The extent of PMN membrane-associated MPO was elevated in patients with acute inflammatory vascular disease compared with healthy individuals. Isolated PMNs bound free MPO by a CD11b/CD18 integrin-dependent mechanism. PMNs exposed to MPO were characterized by increased tyrosine phosphorylation and p38 mitogen-activated protein kinase activation. Also, nuclear translocation of NFkappaBin PMN was enhanced after incubation with MPO, as was surface expression of CD11b. Binding of PMN to MPO-coated fibronectin surfaces amplified PMN degranulation, as evidenced by increased release of MPO and elastase. MPO also augmented PMN-dependent superoxide (O(2)(*-)) production, which was prevented by anti-CD11b antibodies, but not MPO inhibitors. Collectively, these results reveal that binding of MPO to CD11b/CD18 integrins stimulates PMN signaling pathways to induce PMN activation in a mechanism independent of MPO catalytic activity. These cytokine-like properties of MPO thus represent an additional dimension of the proinflammatory actions of MPO in vascular disease.
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PMID:Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. 1562 14

p66(Shc) regulates both steady-state and environmental stress-dependent reactive oxygen species (ROS) generation. Its deletion was shown to confer resistance to oxidative stress and protect mice from aging-associated vascular disease. This study was aimed at verifying the hypothesis that p66(Shc) deletion also protects from diabetic glomerulopathy by reducing oxidative stress. Streptozotocin-induced diabetic p66(Shc) knockout (KO) mice showed less marked changes in renal function and structure, as indicated by the significantly lower levels of proteinuria, albuminuria, glomerular sclerosis index, and glomerular and mesangial areas. Glomerular content of fibronectin and collagen IV was also lower in diabetic KO versus wild-type mice, whereas apoptosis was detected only in diabetic wild-type mice. Serum and renal tissue advanced glycation end products and plasma isoprostane 8-epi-prostaglandin F2alpha levels and activation of nuclear factor kappaB (NF-kappaB) were also lower in diabetic KO than in wild-type mice. Mesangial cells from KO mice grown under high-glucose conditions showed lower cell death rate, matrix production, ROS levels, and activation of NF-kappaB than those from wild-type mice. These data support a role for oxidative stress in the pathogenesis of diabetic glomerulopathy and indicate that p66(Shc) is involved in the molecular mechanism(s) underlying diabetes-induced oxidative stress and oxidant-dependent renal injury.
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PMID:Deletion of p66Shc longevity gene protects against experimental diabetic glomerulopathy by preventing diabetes-induced oxidative stress. 2906 98

The largest cause of mortality in the Western world is atherosclerotic vascular disease. Many of these diseases require synthetic vascular grafts; however, their patency rate is only 30% in small (<6 mm) diameter vascular grafts after 5 years of implantation. In an effort to increase small diameter vascular graft success, researchers have been designing random nanostructured surface features which enhance vascular cell functions. However, for the present study, highly-controllable, nanostructured features on poly(lactic-co-glycolic acid) (PLGA) surfaces were formulated. To create ordered nanostructured roughness on PLGA surfaces, either 500, 200, or 100 nm polystyrene nanospheres were separately placed onto mica. These were then used as a template for creating an inverse poly(dimethylsiloxane) mold which was utilized to cast PLGA. Compared to all other PLGA films formulated, AFM results demonstrated greater initial fibronectin spreading on PLGA which possessed spherical 200 nm features. Compared to smooth PLGA, PLGA with 500 or 100 nm surface features, results further showed that PLGA with 200 nm spherical features promoted vascular cell (specifically, endothelial, and smooth muscle cell) adhesion. In this manner, the present study demonstrated a specific nanometer surface feature size that promoted fibronectin spreading and subsequent vascular cell adhesion; criteria critical to vascular graft success.
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PMID:PLGA nanometer surface features manipulate fibronectin interactions for improved vascular cell adhesion. 1718 86

This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM-together called spontaneous preterm births-are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.
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PMID:Epidemiology and causes of preterm birth. 1817 78

Vascular smooth muscle cell (VSMC) proliferation, migration, and matrix protein accumulation play important roles in the development and progression of vascular disease including diabetic vascular complications and chronic allograft vasculopathy. Mycophenolic acid (MPA) inhibits various mesenchymal cell proliferation and matrix protein accumulation and reactive oxygen species (ROS). In this study, we investigated the effects of MPA on high glucose (HG)-induced fibronectin secretion and the role of ROS in rat VSMCs. Primary cultured rat VSMCs from Sprague-Dawley rats were exposed for 1 hour before stimulation with media containing 5.6 mmol/L glucose (low glucose [LG]), 30 mmol/L mannitol (M), or 30 mmol/L glucose (HG) with or without MPA (0.1-10 micromol/L) or N-acetylcysteine (NAC; 5 mmol/L). Fibronectin secretion was measured by Western blot analysis and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry. HG significantly increased fibronectin secretion by 1.7-fold. The increment of DCF-sensitive cellular ROS was 1.5-fold at 1 hour by HG. MPA at concentrations above 1 micromol/L effectively inhibited HG-induced fibronectin secretion and cellular ROS in a dose-dependent manner. NAC at 5 mmol/L also inhibited HG-induced rat VSMC activation. These results suggested that MPA inhibits HG-induced VSMC activation partially through inhibiting cellular ROS.
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PMID:Effects of mycophenolic Acid on high glucose-induced fibronectin secretion and cellular reactive oxygen species in rat vascular smooth muscle cells. 1837 4

Patients on hemodialysis (HD) are prone to atherosclerotic cardiovascular complications. In an attempt to determine the significance of several atherosclerotic and thrombogenic parameters as risk factors for atherothrombotic cardiovascular disease (CVD) in these patients, we compared two groups of non-diabetic HD patients matched for age and sex, selected according to the absence (group 1, n = 30) or presence (group 2, n = 30) of symptomatic atherothrombotic vascular disease affecting the coronary, cerebral, or peripheral arteries. Duration of HD, primary renal disease (PRD), presence of hypertension, EPO treatment, and smoking habits were recorded. Serum total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, TC/HDL-C ratio, lipoprotein(a) (Lp(a)), fibrinogen (FG), plasminogen (PLG), fibronectin (FN), and hematocrit (HCT) were measured pre-HD in a midweek session. The same blood parameters were also assessed in twenty matched clinically healthy subjects (controls). None of the blood parameters differed between groups 1 and 2, except for serum Lp(a) and FN, which were higher in group 2 (p = 0.005 and p = 0.041, respectively). Both groups were not different regarding PRD, duration of HD, and EPO treatment, but the presence of hypertension and smoking habits were more common in group 2 (p = 0.008 and p = 0.045, respectively). Moreover, multiple stepwise logistic regression analysis with Lp(a), FN, hypertension, and smoking showed that the presence of hypertension (p = 0.016) and the Lp(a) (p = 0.027) and FN (p = 0.024) levels, but not smoking, were independent predictors for the presence of atherothrombotic CVD. Our results suggest that hypertension, abnormal lipid particles, and thrombogenic proteins may contribute to the high prevalence of CVD in HD patients.
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PMID:Cardiovascular risk factors in non-diabetic hemodialysis patients: a comparative study. 1921 4

Fibronectin is an extracellular matrix protein found only in vertebrate organisms containing endothelium-lined vasculature and is required for cardiovascular development in fish and mice. Fibronectin and its splice variants containing EIIIA and EIIIB domains are highly upregulated around newly developing vasculature during embryogenesis and in pathological conditions including atherosclerosis, cardiac hypertrophy, and tumorigenesis. However, their molecular roles in these processes are not entirely understood. We review genetic studies examining functions of fibronectin and its splice variants during embryonic cardiovascular development, and discuss potential roles of fibronectin in vascular disease and tumor angiogenesis.
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PMID:Fibronectins in vascular morphogenesis. 1921 55


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