Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum amyloid A (SAA), the precursor protein in inflammation-associated reactive amyloidosis (AA-type), is an acute phase reactant whose level in the blood increases in response to various insults. It is expressed in the liver, but its physiological role is not well understood. Recently, a broader view of SAA expression and function has been emerging. Expression studies show local production of SAA proteins in histologically normal, atherosclerotic, Alzheimer, inflammatory, and tumor tissues. Binding sites in the SAA protein for high density lipoproteins, calcium, laminin, and heparin/heparan-sulfate were described. Adhesion motifs were identified and new functions, affecting cell adhesion, migration, proliferation and aggregation have been described. These findings emphasize the importance of SAA in various physiological and pathological processes, including inflammation, atherosclerosis, thrombosis, AA-amyloidosis, rheumatoid arthritis, and neoplasia. In addition, recent experiments suggest that SAA may play a "housekeeping" role in normal human tissues.
 ...
PMID:Expression and function of serum amyloid A, a major acute-phase protein, in normal and disease states. 1060 7

Migration of vascular smooth muscle cells (VSMC) is a key event in the formation of neointima during atherosclerosis. Fura-2 loaded VSMCs were used to investigate calcium homeostasis during cell migration. Multiple spontaneous transient increases in cytosolic free calcium [Ca(2+)](i)were observed in single human VSMCs migrating on type I collagen. Such [Ca(2+)](i)transients were dependent on the presence of serum or PDGF-BB. Removal of serum, or loading cells with BAPTA, abolished the transients and decreased cell migration speed. The transients were not affected by disruption of cell polarization by dihydrocytochalasin B. Adhesion was used to investigate the specific role of cell-substrate interactions in the generation of transients. Transients are seen in VSMCs adhering either on collagen or on poly-L-lysine, suggesting that generation of transients is not strictly dependent on integrins. Buffering [Ca(2+)](i) with BAPTA led to accumulation of (beta)1 integrins at the cellular tail, and to increased release of integrin on the extracellular matrix. These results demonstrate a role for [Ca(2+)](i) transients in the rapid, serum-dependent migration of VSMCs. These [Ca(2+)](i)transients are present in migrating VSMCs only when two simultaneous events occur: (1) substrate independent spreading and (2) stimulation of cells by serum components such as PDGF-BB.
 ...
PMID:Migration of human vascular smooth muscle cells involves serum-dependent repeated cytosolic calcium transients. 1065 58

Adhesion of leukocytes to endothelial cells via cell adhesion molecules (CAMS) is thought to be pivotal in the initiation of atherosclerosis. As patients with familial hypercholesterolaemia (FH) are known to develop severe, premature coronary artery disease (CAD), we investigated the usefulness of soluble forms of CAMS namely vascular cellular adhesion molecule-1 (VCAM), intercellular cell adhesion molecule-1 (ICAM) and E-selectin as predictive markers of the presence and severity of atherosclerosis in this patient group. Twenty heterozygous FH patients without CAD; 24 heterozygous FH patients with CAD; 17 homozygous FH patients without documented CAD; nine homozygous FH patients with overt CAD; and 50 healthy controls were studied. Carotid artery intima media thickness (IMT) was also measured in the homozygous patients. Levels of the adhesion molecules VCAM, ICAM and E-selectin were not significantly elevated in homozygous FH patients and heterozygous FH patients, both with and without CAD, compared to the normal control subjects. In addition the range of results was so wide and the overlap of values with normal controls so great, that the use of an individual level of either VCAM, ICAM or E-selectin was not predictive of either the presence or degree of atherosclerosis in the FH subjects.
 ...
PMID:Cell adhesion molecules - can they be used to predict coronary artery disease in patients with familial hypercholesterolaemia? 1069 26

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
 ...
PMID:Endothelial function and hemostasis. 1079 71

E-selectin, a member of the selectin family of adhesion molecules, is thought to play an important role in leukocyte-endothelial (EC) interactions during inflammation and atherosclerosis. To critically examine the role of E-selectin in leukocyte-EC interactions in the vascular system, we created a recombinant adenoviral vector containing a human E-selectin cDNA (AdRSVE-sel) and examined the effect of AdRSVE-sel in an ex vivo vascular model of a rat aortic segment. A segment of abdominal aorta was isolated from a male Sprague-Dawley rat transduced with AdRSVE-sel ex vivo. After 72 h, surface expression of transduced E-selectin in the segment was confirmed by Western blotting and immunohistochemistry using anti-E-selectin mAb. Aortic segments were connected to a perfusion system and the adhesion of human polymorphonuclear neutrophils (PMN), and a human monocytic cell line (THP-1) to the EC surface was studied in the presence of a physiological level of flow (0.85 ml/min, approximate luminal surface shear stress=1.76 dyn/cm2). Adhesion of PMN was assessed by scanning electron microscopy and quantified using fluorescently labeled PMN. AdRSVE-sel transduced aortic segments mediated significantly more PMN and THP-1 adhesion than control segments transduced with AdRSVLacZ. Pretreatment of AdRSVE-sel transduced aortic segments with anti-E-selectin mAb inhibited PMN adhesion significantly, as well as THP-1. These data indicate that human E-selectin expressed in rat aortic segments can support the adhesion of human PMN as well as THP-1 under physiological flow conditions. This genetically modified, excised, vascular-segment model provides a useful tool for the study of leukocyte recruitment in the vascular system.
 ...
PMID:Adenoviral transduction of human E-selectin into isolated, perfused, rat aortic segments: an ex vivo model for studying leukocyte-endothelial interactions. 1107 8

Adhesion of circulating cells to the vascular endothelium is an early step in the development of atherosclerosis. Diabetic patients have a 2-4 fold increased risk for the development of atherosclerosis. Expression of adhesion molecules is increased in diabetes. These molecules may contribute to accelerated atherosclerosis in diabetes. Three main groups of adhesion molecules have been identified: integrins, selectins and members of the immunoglobulin superfamily. The modulation of expression and activity of adhesion molecules may play an important role in the prevention and treatment of atherosclerosis. This article summarises the characteristics and the role of these molecules in atherosclerosis and diabetes.
 ...
PMID:[The role of adhesion molecules in atherosclerosis and diabetes mellitus]. 1112 80

Adhesion and transmigration of leukocytes into arterial walls occurs after vascular injury and may play a role in the development of atherosclerosis and restenosis. This protocol presents a simple, rapid method for quantifying leukocyte adhesion to artery segments ex vivo. The procedure involves isolating leukocytes from rabbit whole blood and labelling with the gamma-emitting isotope 51Cr. Labelled leukocytes are added to open rings of subclavian artery taken from the same rabbit. After gamma counting, percentage leukocyte adhesion can be calculated with reference to a sample containing a quantity of labelled leukocytes equivalent to that which was added to the artery. Leukocyte adhesion was increased by L-NAME, thrombin and increasing incubation time and decreased by low temperatures. In addition, leukocyte adhesion was found to be increased following a vascular stretch injury performed in vitro. This protocol offers a number of advantages: the rapidity of the leukocyte isolation and labelling; the small quantity of leukocytes required; the ability to use autologous leukocytes; the applicability to whole arteries and arteries injured in vitro or in vivo, allowing the effects of vascular injury on leukocyte adhesion to be studied.
 ...
PMID:Validation of a technique to measure leukocyte adhesion to arterial segments: effects of drug treatments. 1168 53

Adhesion of leukocytes to the vascular endothelium is an early event in inflammation. Since cell-cell signaling may be an important stimulus for endothelial activation, we focused in this study on the role of contact-mediated activation by T lymphocytes of endothelial cells (EC). T lymphocytes were cultured with anti-CD3 monoclonal antibody or in the presence of a combination of TNF-alpha, interleukin (IL)-6, and IL-2, prior to fixation and coculture with human umbilical vein EC. Fixed, activated (anti-CD3- or cytokine-stimulated), but not unstimulated T cells, induced release of monocyte chemotactic protein-1, IL-8, and IL-6 by EC in a contact-dependent manner. Moreover, expression of tissue-factor antigen and activity was also significantly increased. Addition of anti-CD40 ligand antibody abolished T cell-induced activation of EC. Our data suggest that contact-mediated activation of EC by T cells, involving ligand:counter ligand interactions such as CD40:CD40 ligand, may represent a novel pathogenic mechanism of progression in inflammatory diseases such as atherosclerosis or rheumatoid arthritis.
 ...
PMID:T cell-mediated signaling to vascular endothelium: induction of cytokines, chemokines, and tissue factor. 1192 53

The early stages of atherosclerosis are characterized by increased endothelial cell (EC) surface expression of leukocyte adhesion molecules (LAMs). Ultrasound detection of acoustically active LAM-targeted microbubbles might provide a means to noninvasively assess the functional status of the endothelium. Toward this end, a lipid-based perfluorobutane-filled microbubble was synthesized with various densities of anti-ICAM-1 monoclonal antibodies conjugated to the bubble shell. We hypothesized that modulating the surface antibody density would permit regulation of the adhesion characteristics of the microbubbles, and that microbubble adhesion would be dependent on local wall shear rate. Coverslips of cultured human coronary artery ECs were exposed to microbubbles with various surface antibody densities (1%, 5%, 10%, 50%, 75%, and 100% of maximum coverage) at various wall shear rates (100, 175, 250, 350, and 500 s-1) in a parallel plate perfusion chamber. ECs were either normal or activated by interleukin-1 beta to overexpress ICAM-1. Adhesion was greater to activated vs. normal ECs (p < 0.001), increased with increasing surface antibody density (p < 0.01), and decreased with increasing wall shear rate (p = 0.02). We conclude that shell antibody density and wall shear rate are critical parameters controlling differential microbubble adhesion. This phenomenon might ultimately permit imaging of clinically relevant LAM expression in vivo.
 ...
PMID:Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium. 1244 62

Atherosclerosis is the most common disease in the industrialised world and by 2020 is predicted to be the number 1 cause of death worldwide. It is a disease of the intima and media of small to medium sized arteries that develop slowly over many years. A number of risk factors for atherosclerosis have been identified, some of these are reversible and some are not. Most prominent amongst these is an elevated level of plasma cholesterol. The lowering of cholesterol reduces the risk of heart attacks, strokes and all forms of atherosclerotic vascular disease. Nonetheless, 70% of patients go on to get symptomatic disease. The disease process sets off an inflammatory response involving the vascular endothelium and both T and B cells of the immune system. Adhesion molecules are induced and proinflammatory cytokines and growth factors are produced by cells that orchestrate the atherosclerotic process. Narrowing the lumen of the artery leads to ischaemic symptoms. Within lesions under the influence of proteolytic enzymes released from activated macrophages (or foam cells--the hallmark of atherosclerosis) the centre of the plaque becomes liquefied to take on it's characteristic "gruel" like appearance. The shoulders of such plaque weaken and it becomes prone to rupture. Plaque rupture may lead to catastrophic thrombosis of coronary or cerebral arteries. The large amounts of tissue factor produced by macrophages make this a particularly likely event. On ulcerated plaques adherent platelets and thrombus create showers of emboli leading to ischaemic attacks. Like the effective treatment of LDL and it's role in the prevention of ischaemic attacks there has been a move to develop new drugs that raise HDL. The discovery of the role of a new class of ABC transporter, defective in Tangiers disease, responsible for cholesterol efflux from peripheral cells including the macrophage has created great excitement around ABC1 as a drug target. New areas, new possible targets and new genetic and genomic approaches will be discussed.
 ...
PMID:The pathogenesis of atherosclerosis and new opportunities for treatment and prevention. 1259 6


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