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

The participation of leukocytes in the development of vascular disorders has been observed under various circumstances. Leukocyte activation occurs in extracorporeal blood circulation which lead to a pulmonary vascular sequestration and respiratory distress syndrome. Leukocytes could act on vascular components through at least two different pathways by releasing free oxygen radicals and proteases or by producing mediators such as interleukin 1, Tumor necrosis alpha, leukotrienes. Monocytes macrophages are present in the vascular wall at a very early stage of atherosclerosis. A majority of foam cells have been identified as macrophages loaded with lipids. Lymphocytes and monocytes are present in the atherosclerotic plaque. Leukocytes are also observed in the inflammatory lesion of vasculitis and experimentally activated lymphocytes can induce vasculitis. The molecular bases of leukocyte-endothelium interactions have been determined, and imply specialized molecules. Leukocyte Adhesion Molecule (LeucAM) appear to play a crucial role in leukocyte adhesion. On the endothelial cell side, endothelial cell adhesion molecule, intercellular adhesion molecule are receptors for leukocytes adhesion. They have been recently fully characterized. The better knowledge of leukocyte-vascular wall interactions offers new possible target for therapeutic agents.
Ann Cardiol Angeiol (Paris) 1991 Mar
PMID:[Leukocytes and vascular lesions]. 204 28

Chronic inflammatory cells are key components in the progression of atherosclerotic plaques and restenosis after coronary angioplasty. Adhesion molecules are fundamental in inflammatory processes. Therefore, the distributions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM) were investigated in directional coronary atherectomy specimens obtained from 14 patients, in 6 with acute coronary syndromes (myocardial infarction and unstable angina within 1 month), 6 with old myocardial infarction and 2 with stable effort angina. There were eight primary lesions and six restenotic lesions. Atherectomy tissue fragments were snap frozen and cut into 4 microns thick cryostat sections for immunohistochemical staining by avidin-biotin complex immunoperoxidase techniques using adhesion molecule specific monoclonal antibodies BBIG-I1 (ICAM-1) and BBIG-V1 (VCAM). The cells of lesions were characterized in sequential sections by macrophage marker KP1 (CD68), endothelial marker JC/70A (CD31), and smooth muscle cell marker 1A4 (alpha-smooth muscle actin). Four restenotic lesions that had undergone a prior balloon angioplasty within a few months consisted of intimal proliferation and the other lesions were atherosclerotic plaque. Macrophage-rich areas were seen in the lesions from acute coronary syndromes and/or early restenotic lesions. Expression of ICAM-1 or VCAM was strongly associated with macrophage-rich areas, but VCAM staining was weaker than ICAM-1 except in one restenotic lesion. Macrophages that express ICAM-1 and/or VCAM may be important in the unstable plaques and restenotic lesions related to disease activity of ischemic heart disease.
J Cardiol 1995 Sep
PMID:[Immunohistochemical analysis of adhesion molecules in directional coronary atherectomy specimens]. 747 44

Adhesion molecules have been demonstrated immunohistochemically on smooth muscle cells in atherosclerotic plaques. In endothelial cells cytokines are potent modulators of adhesion molecule expression. We therefore investigated the effects of cytokines on adhesion molecule expression on cultured human coronary and pulmonary smooth muscle cells by cell ELISA and confocal microscopy. Human coronary and pulmonary smooth muscle cells expressed ICAM-1 and VCAM-1 but not E-selectin. ICAM-1 expression was upregulated by TNF alpha, Il-1 beta and IFN-gamma. VCAM-1 expression was increased by TNF alpha and weakly by Il-1 beta, IFN-gamma had no effect on VCAM-1 expression. Cytokine effects on ICAM-1 and VCAM-1 were based on de novo synthesis. These results demonstrate that cytokines regulate ICAM-1 and VCAM-1 expression on human coronary and pulmonary smooth muscle cells. These effects may play an important role in the immune mechanisms in atherosclerosis.
J Mol Cell Cardiol 1995 Dec
PMID:Modulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on human coronary smooth muscle cells by cytokines. 882 78

Recent investigations have reanimated the view that there exists a possible link between atherosclerosis and inflammation. Adhesion of monocytes as well as T lymphocytes to the arterial endothelial surface, followed by their migration into the subendothelial space is a hallmark for experimental animals fed an atherogenic diet. Human studies show identical features in the arterial wall to the animal models of atherosclerosis. The recruitment of leukocytes into areas of inflammation is mediated by interacting sets of cell adhesion molecules. In atherosclerosis, focal expression of key adhesion molecules particularly triggered by plasma atherogenic lipoproteins has been detected, and these molecules may mediate the recruitment of mononuclear cells to the plaque. Among these adhesion molecules, ICAM-1, a protein of the Ig superfamily, and one of the ligands for LFA-1 have been suggested to play an important role in atherogenesis. In diet-induced hypercholesterolemic rats, we found that ICAM-1 expression is up-regulated mainly in lesion-prone areas of the aorta during the early stages of atherogenesis. Increased ICAM-1 expression was associated with a marked monocyte and T lymphocyte intimal recruitment. Further immunohistochemical studies have demonstrated that LFA-1 is expressed by more than 85% of macrophages in the lesions, and their presence therefore may point toward the involvement of the LFA-1/ICAM-1 receptor ligand pathway in the recruitment of mononuclear cells in the lesions. In order to verify this hypothesis, systemic administration of blocking antibodies was attempted; injection of anti-ICAM-1/LFA-1 monoclonal antibodies significantly reduced macrophage adherence and their emigration into the intima. Our current study suggests that ICAM-1 may act as an "athero-ELAM" for mononuclear cell intimal recruitment during atherogenesis.
Int J Cardiol 1998 Oct 01
PMID:Atherosclerosis and inflammation mononuclear cell recruitment and adhesion molecules with reference to the implication of ICAM-1/LFA-1 pathway in atherogenesis. 995 2

Adhesion molecules are key molecules for inflammatory cardiovascular diseases and are known to be up-regulated by inflammatory cytokines. However, the role of adhesion molecules in the cytokine-induced myocardial dysfunction in vivo remains unclear. This role was examined in our novel canine model, in which chronic treatment of the heart with IL-1 beta-bound microspheres (MS), but not control MS, causes sustained myocardial dysfunction in vivo. The expression of P-selectin (mRNA and immunoreactivity) was more prominent in the IL-1 beta group than in the control group (treated with control MS alone) after MS injection. The extent of neutrophil infiltration and myocardial myeloperoxidase (MPO) activity were significantly increased in the IL-1 beta group (P < 0.01). Pre-treatment with SLeX-OS (a novel oligosaccharide analog of sialyl LewisX) or PB1.3 (a monoclonal antibody to P-selectin) prevented the myocardial dysfunction and significantly suppressed the neutrophil infiltration and the increase in myocardial MPO activity induced by IL-1 beta (P < 0.01 each). These results indicate that adhesion molecules play an important role in the pathogenesis of the cytokine-induced sustained myocardial dysfunction in dogs in vivo.
J Mol Cell Cardiol 1998 Dec
PMID:Inhibition of adhesion molecules markedly ameliorates cytokine-induced sustained myocardial dysfunction in dogs in vivo. 999 May 35

Neutrophil adhesion to coronary endothelium is a key event for cardiac reperfusion injury. Adhesion is proposed to be a multi-step event, consisting of selectin-mediated rolling, chemotactic activation, and subsequent integrin-mediated firm attachment. However, it is not clear whether this sequence also occurs in the coronary circulation with its unique hemodynamic properties (turbulent flow, flow reversal). We have studied neutrophil adhesion in the coronary system of isolated perfused guinea pig hearts under basal and reperfusion conditions (15 min global ischemia). Adhesion was manipulated by an anti-CD18 antibody (blocking firm adhesion) and fucoidin (reducing rolling). Neutrophil behavior during coronary passage was assessed by measurement of CD11b expression, forward scatter (FSC, indicating polarization), and sideward scatter (SSC, measure for granularity) via flow cytometry. Adhesion rose from 21 % (basal) to 35 % after ischemia. Anti-CD18 decreased adhesion to 11 % and 14 %, respectively; fucoidin altered only the postischemic increase (23 %). CD11b was unchanged by passage through the non-ischemic coronaries, but rose postischemically (139 % increase). CD18 blockade did not reduce the postischemic rise of CD11b, while fucoidin was inhibitory (24 % increase). FSC did not differ between controls and ischemic hearts in any group, while SSC decreased most in postischemic hearts after CD18 blockade. Blockade of rolling and of firm attachment both reduce neutrophil retention, while only inhibition of rolling reduces intracoronary activation. Thus, rolling seems to be mandatory for endothelial-leukocyte communication in the coronary system.
Basic Res Cardiol 2002 Sep
PMID:Selectin-mediated rolling of neutrophils is essential for their activation and retention in the reperfused coronary system. 1220 Jun 35

Uptake of oxidized low-density lipoprotein (ox-LDL) by endothelial cells is a critical step for the initiation and development of atherosclerosis. Adhesion molecules are inflammatory makers, which are upregulated by ox-LDL and play a pivotal role in atherogenesis. A number of studies suggest that fish and its constituents can reduce inflammation and decrease atherosclerosis. We hypothesized that fish oil constituents namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce expression of adhesion molecules induced by ox-LDL. Cultured human coronary artery endothelial cells (HCAECs) were incubated with ox-LDL for 24 h. Parallel groups of cells were pretreated with DHA or EPA (10 or 50 microM) overnight before incubation with ox-LDL. Ox-LDL markedly increased the expression of P-selectin and intracellular adhesion molecule-1 (ICAM-1) (both protein and mRNA) in HCAECs, and enhanced the adhesion of monocytes to the cultured HCAECs. Both EPA and DHA decreased ox-LDL-induced upregulation of expression of P-selectin and ICAM-1, and the enhanced adhesion of monocytes to HCAECs. To determine the role of protein kinase B (PKB) as an intracellular-signaling pathway, HCAECs were treated with the PKB upstream inhibitor wortmannin (100 nM) or transfected with plasmids encoding dominant-negative mutants of PKB (PKB-DN) before treatment with DHA. Ox-LDL alone downregulated the activity of PKB; DHA attenuated this effect of ox-LDL, and both wortmannin and PKB-DN blocked the effect of DHA. The present study in human coronary endothelial cells suggests that both EPA and DHA attenuate ox-LDL-induced expression of adhesion molecules, and the adhesion of monocytes to HCAECs by modulation of PKB activation. These effects may be important mechanisms of anti-atherosclerotic effects of fish and fish oils.
J Mol Cell Cardiol 2003 Jul
PMID:EPA and DHA attenuate ox-LDL-induced expression of adhesion molecules in human coronary artery endothelial cells via protein kinase B pathway. 1281 67

Adhesion molecules play an important role in the development and course of coronary atherosclerosis. In this study, soluble forms of vascular cell adhesion molecule (VCAM-1) intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were evaluated in patients with various clinical presentations of coronary atherosclerosis and compared them to those with angiographically documented normal coronary arteries. Venous plasma samples were collected from 43 patients with acute myocardial infarction (AMI), 45 with unstable angina pectoris (UAP), 34 with stable angina pectoris (SAP) and 29 subjects with normal coronary arteries (control). The VCAM-1 level was significantly higher in patients with AMI (mean +/- SEM; 799.8 +/- 26.3 ng/ml) than those with UAP (644.2 +/- 26.7 ng/ml) and SAP (526 +/- 32.5 ng/ml) and controls (270 +/- 26.8 ng/ml). In patients with UAP, VCAM-1 was found to be significantly elevated as compared to the SAP group and controls. VCAM-1 level was also higher in SAP group than the controls. Serum levels ICAM-1 were similar among patients with AMI (424.1 +/- 15.2 ng/ml), UAP (403 +/- 12.3 ng/ml) and SAP (381.2 +/- 16.2 ng/ml); however, levels of ICAM-1 was significantly elevated in these groups as compared to the controls (244.3 +/- 11). The mean level of E-selectin was not different in AMI and UAP groups (47.2 +/- 2.2 vs. 42.6 +/- 2.1 ng/ml; respectively). However, it was significantly higher in acute coronary syndrome groups as compared to SAP (33.4 +/- 2.3 ng/ml) and control subjects (30.7 +/- 1.9 ng/ml). Serum levels of E-selectin were similar in SAP group and controls. For P-selectin, no significant difference was observed between AMI and UAP groups (187.5 +/- 7.2 vs. 181.7 +/- 4.7 ng/ml; respectively), however, it was significantly higher in both groups as compared to SAP group (146.1 +/- 7.4 ng/ml) and controls (108 +/- 6.6 ng/ml). Serum level of P-selectin was significantly higher in patients with SAP than the control group. In conclusion, determination of serum VCAM-1, E-selectin and P-selectin levels seems more useful for detecting coronary plaque destabilization.
Int J Cardiol 2004 Aug
PMID:Levels of soluble adhesion molecules in various clinical presentations of coronary atherosclerosis. 1526 39

Adhesion of mononuclear cells to the vascular endothelium and their subsequent transmigration into the arterial wall represent key events in the pathogenesis of arteriosclerosis. In previous studies we have shown that high density lipoproteins (HDL) and the HDL-associated sphingosylphosphorylcholine (SPC) have the ability to suppress the TNF-alpha-induced expression of endothelial cell E-selectin. However, the current understanding of the mechanism by which HDL reduces the expression of E-selectin is still incomplete. In the present study we show that interaction of the HDL-associated sphingosylphosphorylcholine and sphingosylgalactosyl-3-sulfate (lysosulfatide, LSF) with the G-protein-coupled EDG receptor initiates a signalling cascade that activates the protein kinase Akt and reduces the E-selectin, ICAM-1 and VCAM-1 expression on protein and mRNA level. This signalling cascade is consistently associated with a reduced translocation of TNF-alpha-activated NF-kappaB into the cell nucleus. The suppressor effect of SPC and LSF is completely reverted by inhibition of the phosphatidylinositol- 3-kinase/Akt pathway. We conclude that the antiatherogenic/antiinflammatory effect of lysosphingolipids depends on a competitive interaction of EDG receptor-induced inhibition and TNF-alpha-initiated stimulation of NF-kappaB translocation into the cell nucleus thereby preventing or stimulating inflammatory events in atherogenesis.
Basic Res Cardiol 2006 Mar
PMID:The antiatherogenic and antiinflammatory effect of HDL-associated lysosphingolipids operates via Akt -->NF-kappaB signalling pathways in human vascular endothelial cells. 1645 77

A structural event in the progression of left ventricular (LV) failure is myocardial extracellular matrix (ECM) remodeling. The myocardial fibroblast is a major cell type influencing the ECM, but whether and to what degree specific phenotypic differences in myocardial fibroblasts can be demonstrated to occur in culture with the development of LV failure remains unclear. Adult pigs (25 kg) were used for control myocardial fibroblast preparations (N=5) or following pacing-induced LV failure (N=5; 240 bpm, 3 weeks). LV remodeling occurred with pacing as evidenced by increased LV end diastolic volume (132+/-11 vs. 60+/-4 mL for control; P<0.05). Functional parameters including migration, adhesion, collagen and matrix metalloproteinase release were assessed in fibroblast cultures from passages 1-4. The following findings were consistent with each passage and the results were analyzed with control values set to 100%. Migration of LV failure fibroblasts increased by over 170% (P<0.05). Adhesion to collagen I, laminin and fibronectin was increased by over 160% in LV failure fibroblasts (P<0.05). beta(1) integrin density decreased by 50% in LV failure fibroblasts (P<0.05). Fibrillar collagen release increased by over 130% and matrix metalloproteinase-2 increased by 140% in LV failure fibroblasts (P<0.05). The unique findings of this study are two-fold. First, after a pathological stimulus in-vivo, adult myocardial fibroblasts maintain a consistent phenotype through early passages in-vivo. Second, a differential release of, and response to ECM components occurred in LV failure fibroblasts. Thus, a phenotypic transformation of the myocardial fibroblast occurs with the development of LV failure, which in turn may contribute to matrix remodeling and presents as a potential cellular therapeutic target.
J Mol Cell Cardiol 2006 Apr
PMID:Alterations in cultured myocardial fibroblast function following the development of left ventricular failure. 1651 16


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