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)

Adenovirus vectors are capable of high efficiency in vivo arterial gene transfer, and are currently in use as therapeutic agents in animal models of vascular disease. However, despite substantial data on the ability of viruses to cause vascular inflammation and proliferation, and the presence in current adenovirus vectors of viral open reading frames that are translated in vivo, no study has examined the effect of adenovirus vectors alone on the arterial phenotype. In a rabbit model of gene transfer into a normal artery, we examined potential vascular cell activation, inflammation, and neointimal proliferation resulting from exposure to replication-defective adenovirus. Exposure of normal arteries to adenovirus vectors resulted in: (a) pronounced infiltration of T cells throughout the artery wall; (b) upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in arterial smooth muscle cells; (c) neointimal hyperplasia. These findings were present both 10 and 30 d after gene transfer, with no evidence of a decline in severity over time. Adenovirus vectors have pleiotropic effects on the arterial wall and cause significant pathology. Interpretation of experimental protocols that use adenovirus vectors to address either biological or therapeutic issues should take these observations into account. These observations should also prompt the design of more inert gene transfer vectors.
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PMID:Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointimal hyperplasia. 867 67

Inflammatory processes have been implicated in the formation of senile plaques in the cerebral cortex of patients with dementia of the Alzheimer type (DAT), since several inflammation-induced proteins are present within these plaques. The relation between inflammatory components and other amyloid beta protein (A beta)-containing lesions of the DAT brain [cerebrovascular amyloidosis (CA) and cerebellar senile plaques] is unclear. We studied the distribution of the inflammation-inducible protein intercellular adhesion molecule-1 (ICAM-1) in CA and in senile plaques of the cerebellum, using an immunohistochemical approach. We observed striking differences in ICAM-1 reactivity between the different types of A beta-containing lesions. ICAM-1 was only expressed in classic senile plaques in the granular and Purkinje cell layer of the cerebellum, and not in diffuse senile plaques of the molecular layer. Also, ICAM-1 was not associated with CA; only when the vascular amyloid extended into the neuropil (dyshoric angiopathy) was perivascular ICAM-1 reactivity observed. This is in contrast to the putative primary involvement of inflammation in the formation of cerebrocortical classic and diffuse senile plaques. Our findings indicate that ICAM-1 expression, which may be an indicator of an inflammatory reaction, is induced in the neuropil depending on the specific site of A beta production.
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PMID:Differential expression of intercellular adhesion molecule-1 (ICAM-1) in the A beta-containing lesions in brains of patients with dementia of the Alzheimer type. 878 60

Secondary prevention of atherosclerosis, especially before the onset of symptoms, appears desirable and could be possible with a serum marker detecting atherosclerosis. Circulating, shedded forms of adhesion molecules may serve as such because their expression is upregulated in atherosclerotic plaques. In 52 patients with peripheral arterial vascular disease (Fontaine class IIa, 7 patients; class IIb, 29 patients; and class III, 16 patients), the extent of atherosclerosis was evaluated on the basis of angiograms of a large portion of the arterial system. The area diseased by atherosclerosis was determined by the percentage of vessel wall irregularities of the following calculated segments: aorta (distal from the kidney arteries), common iliac artery, external iliac artery, common femoral artery, lateral circumflex femoral artery, and popliteal artery. The maximal surface area that could exhibit atherosclerotic changes was 250 cm2. The serum concentration of circulating vascular cell adhesion molecule-1 (VCAM-1) correlated with the extent of atherosclerosis (r = .8, P < .001). In contrast, circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin (as markers for endothelial cell damage) did not correlate with the extent of atherosclerosis. Furthermore, circulating VCAM-1 could be used to indicate stages of atherosclerosis with a high degree of statistical significance. The potential bias of factors such as age, diabetes mellitus, hypercholesterolemia, arterial hypertension, renal failure, and history of myocardial infarction on the correlation of circulating VCAM-1 with the extent of atherosclerosis could be excluded by multivariate analysis. These findings suggest an important role of VCAM-1 in atherosclerosis and may serve as the basis for further evaluation of circulating VCAM-1 as a potential serum marker for atherosclerosis.
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PMID:Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin. 910 69

A 22-year-old first man came to our hospital because of dyspnea on exertion in February 1993, and was admitted in September 1994 because of progression of dyspnea. A chest roentgenogram showed diffuse ground-glass-opacities in the middle and lower lung fields, and an elevated diaphragm. Pulmonary-function testing revealed a low %VC and a low diffusing capacity. Examination of a specimen obtained by thoracoscopic lung biopsy revealed usual interstitial pneumonia. Immunohistochemical examinations showed the expression of intercellular adhesion molecule-1 on vascular endothelial cells and on alveolar epithelial cells. Dust inhalation and collagen vascular disease were ruled out and the diagnosis was idiopathic interstitial pneumonia. This condition develops only rarely in patients under 60 years old.
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PMID:[Juvenile onset of idiopathic interstitial pneumonia]. 916 50

A unique peripheral vascular disorder called 'blackfoot disease' is endemic in a limited area on the south-west coast of Taiwan. Clinically, the signs and symptoms of blackfoot disease (BFD) are similar to those of arteriosclerosis and Buerger's disease. A destruction of vascular endothelial cells (ECs) takes place at an early stage in the affected limbs. Currently, the cause of BFD is believed to be artesian drinking water containing a high concentration of arsenic and/or humic substances, although the mechanism of EC destruction is not entirely understood. The purpose of the present study was to examine the factors related to EC damage in BFD. Thus, we investigated the effects of purified IgG collected from patients with BFD (BFD-IgG) and from normal controls (N-IgG) on cultured EC. We found that: (1) EC binding activity of BFD-IgG was significantly higher than that of N-IgG; (2) BFD-IgG, at a concentration higher than 100 microg/ml but not N-IgG, induced concentration-dependent EC cytotoxicity; (3) BFD-IgG at a concentration of 100 microg/ml stimulated neither the release of von Willebrand factor nor the expression of intercellular adhesion molecule-1 by EC. Fluorescent video microscopic examination revealed an increase in transcapillary and interstitial diffusion of nailfold capillary loops in clinically normal fingers of BFD patients. These findings strongly suggested that immunological mechanisms played a significant role in the pathogenesis of BFD. We propose that only persons who produce the IgG anti-endothelial cell antibody are potential victims of BFD.
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PMID:In vitro cytotoxicity of IgG antibodies on vascular endothelial cells from patients with endemic peripheral vascular disease in Taiwan. 956 46

1. We have previously shown a circadian variation in leucocyte activation and endothelial function which may explain why some inflammatory and vascular diseases show a circadian variation in disease activity/ occurrence. 2. We have investigated the circadian variation of two soluble cell adhesion molecules, intercellular adhesion molecule-1 and E-selectin, in 10 healthy volunteers. Soluble intercellular adhesion molecule-1 is released from both activated leucocytes and endothelial cells while soluble E-selectin is released only from activated endothelium. 3. Results show a circadian variation exists for both soluble intercellular adhesion molecule-1 and E-selectin (both P < 0.0001, analysis of variance) with a peak activity at 12:00 h for both measures and a minimum activity at 04:00 h for intercellular adhesion molecule-1 and 00:00 h for E-selectin. 4. These results demonstrate the existence of a diurnal variation in cell adhesion molecules, providing evidence in support of a diurnal pattern in endothelial and leucocyte activation. An alteration in this biological rhythm may help to explain the diurnal variation in disease activity in certain inflammatory and vascular disease states. Furthermore, it stresses the importance of sample time point standardization in clinical studies.
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PMID:A circadian variation exists for soluble levels of intercellular adhesion molecule-1 and E-selectin in healthy volunteers. 968 78

Pentoxifylline used in the treatment of vascular diseases has also some immunological effects. Among of these effects the influence of pentoxifylline on the natural killer cell activity was studied. In in vitro experiments the human natural killer cell cytotoxicity was examined in the presence of pentoxifylline. In our clinical trial we investigated the topic whether this drug has an immunomodulatory effect while administering it for different periods. The natural cytotoxicity of macroangiopathic patients treated with pentoxifylline was compared with the values of healthy controls and patients suffering from vascular disease and obtaining no pentoxifylline therapy. Sixty two macroangiopathic patients and twenty healthy controls were investigated altogether. In the in vitro natural killer cell reaction we found that the pentoxifylline was able to suppress the cytotoxicity at any time of the reaction. The influence of pentoxifylline on natural killer cell activity was neither due to the expression of intercellular adhesion molecule-1, nor to the alteration of membrane fluidity. However, this drug significantly (p < 0.05) decreases the apoptosis of target cells. The natural killer cell activity of patients with chronic pentoxifylline therapy lasting for more than a year was proved to be significantly (p < 0.005) lower. The presence of vascular disease does not influence the natural killer activity by itself. Concluding our results we can state that the suppressing effect of pentoxifylline on natural killer cell activity needs to be taken into consideration in case of clinical diseases where this drug is administered chronically.
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PMID:[In vitro and clinical effect of pentoxifylline on natural killer cell activity]. 980 58

A critical early event in the pathogenesis of occlusive vascular disease is the adhesion of monocytes to endothelial cells. The authors have previously reported that insulin-like growth factor-1 increases monocyte-endothelial cell adhesion and increases the expression of intercellular adhesion molecule-1. In this study, it is hypothesized that the upregulation of intercellular adhesion molecule-1 expression after treatment with insulin-like growth factor-1 is caused by an increase in the transcription of intercellular adhesion molecule-1 in endothelial cells, and that this transcription is regulated, at least in part, by activation of nuclear factor-kappaB. Adherence cell assays were performed using insulin-like growth factor-1 treated human umbilical vein endothelial cells and human monocytes. To determine the role of nuclear factor-kappaB, Western blotting using the anti-p65 (activated portion of nuclear factor-kappaB) was performed on cell lysate of human umbilical vein endothelial cells treated with insulin-like growth factor-1. RT-PCR was performed on RNA extracted from insulin-like growth factor-1-treated human umbilical vein endothelial cells. Intercellular adhesion molecule-1 antibody attenuated the increase in monocyte-endothelial cell adhesion of endothelial cells exposed to insulin-like growth factor-1. We observed an increase in expression of the activated nuclear factor-kappaB p65 protein in response to insulin-like growth factor-1 treatment. Peak increase occurred at 30 min. This effect was sensitive to pretreatment of human umbilical vein endothelial cells with the insulin-like growth factor-1 receptor antibody. Human umbilical vein endothelial cells treated with insulin-like growth factor-1 for 2 and 4 h revealed a significant increase in intercellular adhesion molecule-1 mRNA as compared with untreated human umbilical vein endothelial cells. Tumor necrosis factor-alpha produced a larger increase in intercellular adhesion molecule-1 mRNA expression. These results suggest that insulin-like growth factor-1 enhances intercellular adhesion molecule-1 transcription and activates nuclear factor-kappaB in endothelial cells. The intracellular pathways that increase cell adhesion molecule expression may provide a common link to understanding the monocyte-endothelial cell adhesion that occurs in the early stages of atherosclerosis and restenosis.
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PMID:Insulin like growth factor-1 activates nuclear factor-kappaB and increases transcription of the intercellular adhesion molecule-1 gene in endothelial cells. 1007 67

The methylxanthine derivative pentoxifylline, widely used in the treatment of vascular diseases, also has numerous immunological effects. In in vitro experiments, the human natural killer cell cytotoxicity was investigated in the presence of pentoxifylline. A clinical trial involved an investigation of the natural killer cell activity in patients to whom pentoxifylline had been administered for different periods. The natural cytotoxicity in macroangiopathic patients treated with pentoxifylline was compared with that in healthy controls and that in patients with vascular diseases who did not receive pentoxifylline therapy. A total of 62 macroangiopathic patients and 20 healthy controls were investigated. The natural killer cell activity in patients receiving pentoxifylline therapy for more than a year proved to be significantly lower (P<0.005). The presence of vascular disease did not influence the natural killer activity. In the in vitro cytotoxicity reaction, pentoxifylline at a concentration of 100 microg/ml was found to suppress the natural killer cell cytotoxicity at any stage of the reaction. The influence of pentoxifylline on the natural killer cell activity was not due to inhibition of the expression of intercellular adhesion molecule-1. However, this drug significantly decreases (P<0.05) the apoptosis of target cells. It is presumed that the suppressor effect of pentoxifylline on natural killer cell activity should be taken into consideration in the treatment of clinical diseases where this drug is administered chronically.
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PMID:Suppressive effect of pentoxifylline on natural killer cell activity; experimental and clinical studies. 1020 10

Endothelial cell injury has been implicated in the increased incidence of vascular disease associated with diabetes mellitus. In diabetic humans, elevated plasma von Willebrand Factor (vWF) has been interpreted as an indication of endothelial damage. In contrast, in an animal model of inherited insulin-dependent diabetes, the bio-breeding (BB) rat, plasma vWF levels did not differ from those in age-matched control rats during the first 7 months of diabetes although morphological evidence of mild aortic endothelial alteration or injury was observed. In the present study efforts have been made to define the endothelial alterations in BB diabetic rats compared to controls more precisely over this time period. Thus, adhesion molecules: intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) were evaluated by in situ immunohistochemistry, vWF content was determined by biochemical analysis of aortic extracts and by quantitative immunohistochemistry, plasma vWF levels were measured by ELISA and vWF mRNA by RNAse protection assay. Neither age nor diabetic state significantly affected either the expression of adhesion molecules, or the levels of circulating vWF. Endothelial vWF content was significantly increased in the diabetic vessels, as observed by both approaches but the vWF mRNA content was not different from that in control vessels. Plasma plasminogen activator inhibitor (PAI-1) activity was significantly increased in diabetic animals. In conclusion, endothelial alterations in BB rats associated with diabetes, together with the raised plasma PAI-1 levels, promote the thrombogenic potential of the vessel wall, and are consistent with an increased risk for vascular disease.
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PMID:Aortic endothelial cell von Willebrand factor content, and circulating plasminogen activator inhibitor-1 are increased, but expression of endothelial leukocyte adhesion molecules is unchanged in insulin-dependent diabetic BB rats. 1072 83


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