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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is a complex disease involved in major fatal events such as myocardial infarction and stroke. It is the result of interactions between metabolic, dietetic and environmental risk factors acting on a genetic background that could result in endothelial susceptibility. Our aim was to determine the patterns of expression of adhesion molecules and whether phosphatidylserine is translocated to the cell surface of human umbilical vein endothelial cells (HUVECs) isolated from healthy newborns born to parents with a strong family history of myocardial infarction under TNF-alpha or oxLDL stimulated conditions. Compared to control HUVECs, experimental cords showed: (a) a four-fold increase in VCAM-1 expression under basal conditions, which showed no change after stimulation with the pro-atherogenic factors; (b) a two-fold increase in basal P-selectin expression that reached a 10-fold increase with any of the pro-atherogenic factors; (c) a basal ICAM-1 expression similar to P-selectin that was not modified by the pro-atherogenic molecules; (d) a similar PECAM-1 expression. Unexpectedly, phospathidylserine expression in experimental cord HUVECs was significantly increased (211 817 versus 3354 TFU) but was not associated to apoptotic death as the percentage of dead cells induced by TNF-alpha treatment was very low (0.55 versus 9.87% in control HUVECs). The latter result was corroborated by TUNEL staining. T cell adherence to HUVECs was highly up-regulated in the genetically predisposed samples. The analysis of nonpooled HUVECs, from newborns to family predisposed myocardial-infarction individuals, might represent a useful strategy to identify phenotypical and functional alterations, and hopefully, to take early preventive actions.
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PMID:HUVECs from newborns with a strong family history of myocardial infarction overexpress adhesion molecules and react abnormally to stimulating agents. 1604 34

Cerebral ischemia triggers an inflammatory process involving the infiltration of leukocytes to the parenchyma. Circulating leukocytes adhere to the vascular wall through adhesion molecules. Here we quantified the in vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in the brain, heart and lungs from 6 to 48 h after transient middle cerebral artery (MCA) occlusion in rats, by intravenous injection of a tracer radiolabelled anti-VCAM-1 antibody. The vascular localization of VCAM-1 was verified by immunohistochemistry after in vivo injection of the antibody. Vascular cell adhesion molecule-1 was strongly induced (4-fold at 24 h) in the microvasculature of the ischemic area, and, to a lesser extent, in the contralateral hemisphere and in a remote organ, the heart, but not in the lungs, indicating that the inflammatory process propagates beyond the injured brain. We injected intravenously either blocking doses of anti-VCAM-1 antibodies or control antibodies after MCA occlusion in rats and mice. We evaluated the neurological score in rats, and infarct volume at 2 days in rats and at 4 days in mice. Anti-VCAM-1 did not protect against ischemic damage either in rats or in mice. Vascular cell adhesion molecule-1 blockade significantly decreased the number of ED1 (labeling monocytes /macrophages/reactive microglia)-positive cells in the ischemic rat brain. However, it did not reduce the numbers of infiltrating neutrophils and lymphocytes, and total leukocytes (CD45 positive), which showed a trend to increase. The results show vascular upregulation of VCAM-1 after transient focal ischemia, but no benefits of blocking VCAM-1, suggesting that this is not a therapeutical strategy for stroke treatment.
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PMID:Anti-VCAM-1 antibodies did not protect against ischemic damage either in rats or in mice. 1607 86

To investigate whether serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were related to first stage cancer before diagnosis of cancer, we compared serum levels of these adhesion molecules between pre-clinical cases and controls using a nested case-control study method. Cancer cases were recruited from a cohort database of 1465 participants who completed a baseline questionnaire and provided blood samples, and were followed up from 1989 to 2003. They consisted of 15 individuals who died of cancer and 31 individuals newly diagnosed with cancer during the follow-up period. Controls were subjects who did not suffer from cancer, cerebral apoplexy, diabetes mellitus, liver disease, or myocardial infarction during the follow-up period. Using commercially available enzyme-linked immunosorbent assay (ELISA) kits, we showed that serum levels of sVCAM-1, but not sICAM-1 were elevated in cases with pre-clinical or early cancer. We suggest that elevated serum levels of sVCAM-1 might serve as a possible marker for detecting pre-clinical or early cancer.
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PMID:Serum levels of soluble ICAM-1 and VCAM-1 predict pre-clinical cancer. 1614 89

Chunghyuldan (CHD), a combinatorial drug that has antihyperlipidemic and anti-inflammatory activities, has been shown to improve arterial stiffness and inhibit stroke recurrence in clinical study. To understand the molecular basis of CHD's clinical effects, we explored its effect on cell proliferation and expression of nitric oxide synthase (NOS) and vascular cell adhesion molecule (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Cell number counting and [3H]thymidine incorporation assay demonstrated that nontoxic doses of CHD have an inhibitory effect on DNA synthesis and suppress cell cycle progression of HUVECs. CHD treatment led to a marked induction of NO production through up-regulation of NOS mRNA expression in a dose- and time-dependent manner, whereas it suppressed VCAM-1 expression. CHD inhibition of VCAM-1 expression was totally blocked by pretreatment with the NO synthesis inhibitor L-NMMA, whereas pretreatment with the NO donor DETA-NO further decreased VCAM-1 level in CHD-treated HUVECs, indicating that VCAM-1 regulation by CHD is mediated through increased NO synthesis by CHD. In addition, TNF-alpha-mediated VCAM-1 activation was substantially impeded by CHD treatment. Collectively, our data suggest that anti-inflammatory or anti-hyperlipidemic effects of CHD might be associated with its ability to activate NO production and suppress VCAM-1 expression in human endothelial cells.
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PMID:Chunghyuldan activates NOS mRNA expression and suppresses VCAM-1 mRNA expression in human endothelial cells. 1646 9

Previous studies have demonstrated that polydatin, a crystal component extracted from the root stem of the perennial herbage Polygonum Cuspidatum Sieb.et Zucc, exerts a neuroprotective effect on cerebral injury induced by ischemia/reperfusion. To investigate the possible mechanism of this action, we determined the effects of polydatin on the expression of cell adhesion molecules (CAMs) after ischemia-induced cerebral injury. Rats were treated with polydatin (i.v.) immediately after the operation of middle cerebral artery occlusion (MCAO) for 1 h. It was found that polydatin improved neurological deficits and reduced the volume of brain infarction. In addition, polydatin decreased the levels of CAMs relative to the control (MCAO alone); these included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, L-selectin and Integrins. These results suggest that polydatin exerts protective effects likely via inhibition of the expression of various CAMs; polydatin may be a potential agent for treatment of brain injury associated with stroke.
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PMID:Involvement of cell adhesion molecules in polydatin protection of brain tissues from ischemia-reperfusion injury. 1687 Jan 62

Atherosclerosis is a multifactorial inflammatory disease of blood vessels which decimates one in every three people in industrialized world. Despite the important newest clinical approaches, currently available strategies (e.g. nutritional, pharmacological and surgical) may only restrain the worsening of vascular disease. Since antiproliferative cyclopentenone prostaglandins (CP-PGs) are powerful anti-inflammatory agents, we developed a negatively charged liposome-based pharmaceutical formulation (LipoCardium) that specifically direct CP-PGs towards the injured arterial wall cells of atherosclerotic mice. In the blood stream, LipoCardium delivers its CP-PG contents only into activated arterial wall lining cells due to the presence of antibodies raised against vascular cell adhesion molecule-1 (VCAM-1), which is strongly expressed upon inflammation by endothelial cells and macrophage-foam cells as well. After 4 months in a high-lipid diet, all low-density lipoprotein receptor-deficient adult control mice died from myocardium infarction or stroke in less than 2 weeks, whereas LipoCardium-treated (2 weeks) animals (still under high-lipid diet) completely recovered from vascular injuries. In vitro studies using macrophage-foam cells suggested a tetravalent pattern for LipoCardium action: anti-inflammatory, antiproliferative (and pro-apoptotic only to foam cells), antilipogenic and cytoprotector (via heat-shock protein induction). These astonishing cellular effects were accompanied by a marked reduction in arterial wall thickness, neointimal hyperplasia and lipid accumulation, while guaranteed lifespan to be extended to the elderly age. Our findings suggest that LipoCardium may be safely tested in humans in a near future and may have conceptual implications in atherosclerosis therapy.
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PMID:LipoCardium: endothelium-directed cyclopentenone prostaglandin-based liposome formulation that completely reverses atherosclerotic lesions. 1699 18

This study investigates the ability of a single, low dose of apolipoprotein (apo) A-I, the main lipoprotein of high density lipoproteins (HDL), to inhibit acute vascular inflammation in normocholesterolemic New Zealand White rabbits. Acute vascular inflammation was induced in the animals by placing a non-occlusive, silastic collar around the left common carotid artery. The animals (n=5/group) received a single, low dose infusion of saline or lipid-free apoA-I at the time of, or 3 or 9h after collar insertion. The animals were sacrificed 24h post-collar insertion. Inflammatory markers in the artery wall were quantitated immunohistochemically. The saline-treated animals exhibited substantial pan-arterial inflammation, which was inhibited by a single apoA-I infusion (2 or 8 mg/kg) at the time of collar insertion. A single 8 mg/kg infusion of lipid-free apoA-I administered 3h post-collar insertion reduced neutrophil recruitment into the vessel wall, and MPO expression, as well as endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by >85% (p<0.01 for all). A single 8 mg/kg infusion of lipid-free apoA-I administered 9h after collar insertion decreased VCAM-1 expression, neutrophil infiltration and MPO expression by 88% (p<0.001), 47% (p<0.01), and 90% (p<0.01), respectively. This indicates that a single low dose infusion of apoA-I administered after the onset of acute inflammation in carotid arteries decreases neutrophil infiltration and inhibits neutrophil and endothelial cell activation. These findings have potential implications for treating acute vascular inflammation in conditions such as acute coronary and stroke syndromes.
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PMID:Low dose apolipoprotein A-I rescues carotid arteries from inflammation in vivo. 1758 10

Although statins are being used for secondary prevention of ischemic stroke, recent experimental data have shown new pleiotropic effects of these drugs responsible for their role in neuroprotection. We conducted a pilot, double-blind, randomized, multicenter clinical trial to study for the first time safety and efficacy of simvastatin in the acute phase of ischemic stroke. Simvastatin/placebo was given at 3-12 h from symptom onset to 60 patients with cortical strokes. Efficacy on the evolution of several inflammation markers [interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein, sApo/Fas, tumor necrosis factor-alpha, E-selectin, L-selectin and nitrites+nitrates] and neurological outcome was evaluated at baseline, day 1, 3, 5, 7 and 90. No differences were found amongst the biomarkers studied regarding treatment allocation. Although simvastatin patients improved significantly by the third day (46.4% vs. 17.9%, P = 0.022), a non-significant increase in mortality and greater proportion of infections (odds ratio 2.4, confidence interval 1.06-5.4) in the simvastatin group were the main safety concerns. Therefore, a larger clinical trial is needed to confirm the net benefit of this therapeutic approach.
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PMID:Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial. 1807 96

Cerebrovascular disease is a significant cause of morbidity and mortality in the world. Inflammatory processes induce several pathological responses such as atherosclerosis, which have fundamental roles in stroke in the etiology of ischemic cerebrovascular disease and the pathophysiology of cerebral ischemia. Viral interleukin-10 (vIL-10), a potential anti-inflammatory cytokine, has been studied extensively. However, the efficacy of vIL-10 on cerebrovascular dysfunction is not well known. Our goal in this study was to explore the effect of gene transfer of vIL-10 mediated by adenovirus (Ad/vIL-10) on cerebrovascular function using a model of vasocontraction of isolated basilar artery from mongrel dogs induced by lysophosphatidylcholine (lysoPC), a proinflammatory and atherogenic serum lysophospholipid. To clarify the relation between contraction of basilar aorta and cell adhesion and adhesion molecules, our further study explored effects of Ad/vIL-10 on monocyte-cerebrovascular endothelial cells adhesion and expression of cell adhesion molecule by cultured cerebromicrovascular endothelial cells, bEnd.3, after incubation by lysoPC. Our results showed that Ad/vIL-10 significantly decreased contractive response of basilar aorta produced by lysoPC and augmented vasorelaxation to acetylcholine. Further studies showed the Ad/vIL-10 significantly depressed adherence of monocytes to cerebrovascular endothelial cells and inhibited up-regulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which are bio-markers in inflammatory progress. These data demonstrated the protective effects of Ad/vIL-10 on cerebrovascular dysfunction induced by inflammation, and proved that inhibition of expression of cell adhesion molecules should be one of ways of vIL-10 to protect vascular function during inflammation.
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PMID:Adenoviral gene transfer of viral interleukin-10 protects cerebrovascular impairment induced by lysophosphatidylcholine. 1815 52

In pharmacological doses, nicotinic acid (niacin) reduces myocardial infarction, stroke and atherosclerosis. The beneficial effects of niacin on lipoproteins are thought to mediate these effects. We hypothesized that niacin inhibits oxidative stress and redox-sensitive inflammatory genes that play a critical role in early atherogenesis. In cultured human aortic endothelial cells (HAEC), niacin increased nicotinamide adenine dinucleotide phosphate (NAD(P)H) levels by 54% and reduced glutathione (GSH) by 98%. Niacin inhibited: (a) angiotensin II (ANG II)-induced reactive oxygen species (ROS) production by 24-86%, (b) low density lipoprotein (LDL) oxidation by 60%, (c) tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activation by 46%, vascular cell adhesion molecule-1 (VCAM-1) by 77-93%, monocyte chemotactic protein-1 (MCP-1) secretion by 34-124%, and (d) in a functional assay TNF-alpha-induced monocyte adhesion to HAEC (41-54%). These findings indicate for the first time that niacin inhibits vascular inflammation by decreasing endothelial ROS production and subsequent LDL oxidation and inflammatory cytokine production, key events involved in atherogenesis. Initial data presented herein support the novel concept that niacin has vascular anti-inflammatory and potentially anti-atherosclerotic properties independent of its effects on lipid regulation.
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PMID:Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. 1855 65


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