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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinopathy is a severely disabling complication of diabetes mellitus whose underlying mechanisms are still obscure. The key question is why retinal microvessels are so reactive to the diabetic environment, whereas other microvessels show no evidence of alteration. The answer could lie in the particular structure and location of retinal microvessels since they are composed of, and surrounded by, various types of cells, thereby favouring cell-cell interactions which occur between cells of the capillary wall itself but also with circulating blood cells and retinal neural cells. In the retinal capillary wall, pericytes are in close relation with underlying endothelial cells, and both cell types have close contacts with the capillary basement membrane. Adhesion molecules and cell surface glycoconjugates appear to be the main mediators of interactions between circulating blood cells and capillary endothelial cells, whereas growth factors seem to play a major role in interactions between glial and capillary wall cells in the retina. Biochemical dysfunctions observed in diabetes, such as glycation of proteins and enhanced oxidative stress, could modify these cell-cell and cell-matrix interactions, thereby disturbing the complex cellular organization in which retinal microvessels are embedded. The aim of this review was to provide an overall, nonexhaustive description of some types of cellular interactions that may underlie the pathogenic mechanisms involved in flow and growth changes leading to diabetic retinopathy.
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PMID:Involvement of cell-cell interactions in the pathogenesis of diabetic retinopathy. 905 64

Adhesion molecule expression on peripheral blood leukocytes from diabetic patients with severe retinopathy and age-matched control subjects was assessed. Expression of CD11b, CD18, and L-selectin was measured on granulocytes and lymphocytes in whole blood within 1 hour of blood collection. Adhesion molecule expression was determined at 4 degrees C, 37 degrees C, and after stimulation with one of the chemotactic peptides, N-formyl-methionyl-leucyl-phenyl-alanine or beta-phorbol 12-myristate 13-acetate. There were no differences between diabetics and controls in CD11b expression in neutrophils at 4 degrees C, 37 degrees C, or after N-formyl-methionyl-leucyl-phenylalanine stimulation. However, during stimulation with beta-phorbol 12-myristate 13-acetate, the increase in CD11b expression in neutrophils from patients with diabetes was significantly less than in controls. In neutrophils, there was no difference between the control and diabetic participants in CD18 expression at 4 degrees C, but after warming the cells to 37 degrees C, the expression was significantly higher in patients with diabetes. The difference became even more apparent after N-formyl-methionyl-leucyl-phenyl-alanine stimulation. The increase in CD18 expression after beta-phorbol 12-myristate 13-acetate stimulation of neutrophils was similar in control and diabetic participants. There was no difference in L-selectin expression in neutrophils under any conditions. There was no difference in adhesion molecule expression on lymphocytes under similar conditions. In summary, these observations indicate that integrin expression of neutrophils from patients with diabetes and retinopathy is altered after stimulation with neutrophil-activating agents. The changes were integrin-, stimulus-, and cell-specific, which suggests that the signal transduction mechanisms may be altered in diabetic neutrophils. These alterations may be responsible for abnormal leukocyte/endothelial interactions and microvascular complications in diabetic retinopathy.
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PMID:Alterations in stimulus-induced integrin expression in peripheral blood neutrophils of patients with diabetic retinopathy. 907 29

Tetraspanin protein CD151 is abundant on endothelial cells. To determine whether CD151 affects angiogenesis, Cd151-null mice were prepared. Cd151-null mice showed no vascular defects during normal development or during neonatal oxygen-induced retinopathy. However, Cd151-null mice showed impaired pathologic angiogenesis in other in vivo assays (Matrigel plug, corneal micropocket, tumor implantation) and in the ex vivo aortic ring assay. Cd151-null mouse lung endothelial cells (MLECs) showed normal adhesion and proliferation, but marked alterations in vitro, in assays relevant to angiogenesis (migration, spreading, invasion, Matrigel contraction, tube and cable formation, spheroid sprouting). Consistent with these functional impairments, and with the close, preferential association of CD151 with laminin-binding integrins, Cd151-null MLECs also showed selective signaling defects, particularly on laminin substrate. Adhesion-dependent activation of PKB/c-Akt, e-NOS, Rac, and Cdc42 was diminished, but Raf, ERK, p38 MAP kinase, FAK, and Src were unaltered. In Cd151-null MLECs, connections were disrupted between laminin-binding integrins and at least 5 other proteins. In conclusion, CD151 modulates molecular organization of laminin-binding integrins, thereby supporting secondary (ie, after cell adhesion) functions of endothelial cells, which are needed for some types of pathologic angiogenesis in vivo. Selective effects of CD151 on pathologic angiogenesis make it a potentially useful target for anticancer therapy.
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PMID:Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro. 1702 88

Recent studies have shown a close correlation between advanced diabetic retinopathy and the late stages of atherosclerosis. The purpose of this study was to analyse the association between diabetic retinopathy and early atherosclerotic changes in adolescents with type 1 diabetes. We studied 28 adolescents with type 1 diabetes. Eight patients with nonproliferative retinopathy were compared with the remaining 20 patients, and with 11 healthy controls. The function of endothelium was assessed by measuring flow-mediated dilatation (FMD), the intima-media thickness (IMT) of the common carotid arteries and adhesion molecules (sICAM-1, sVCAM-1, sE-selectin). In the group with retinopathy FMD equalled 7.8+/-4.1% vs. 12.1+/-5.1% in the control group (p=0.04), and in the group without retinopathy, 7.6+/-5.5% (p=0.04 compared to controls). Higher IMT was found in all patients with diabetes in comparison with healthy controls: 0.49+/-0.06 mm vs. 0.42+/-0.03 mm (p=0.001). Patients with retinopathy had a significantly higher value of IMT in comparison not only with controls but also with patients without complications: 0.56+/-0.06 mm vs. 0.47+/-0.03 mm (p=0.0001). Adhesion molecule levels were not changed in patients with retinopathy. Higher IMT was found in adolescents with diabetic retinopathy in comparison with patients without complications, which may suggest that macrovascular changes are more advanced in these patients than in their diabetic peers without retinopathy.
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PMID:The association of early atherosclerosis and retinopathy in adolescents with type 1 diabetes: preliminary report. 1772 51

Adhesion molecules play a significant role in leukocyte migration across the endothelium and are also involved in regulating immune system. It is shown that diabetic patients have an increase of soluble adhesion molecules (sICAM-1, sICAM-2, sVCAM-1, sE-selectin, sL-selectin, sP-selectin) considered an integral part of inflammatory state. This inflammation is responsible for the increased cardiovascular risk of these patients. There is a close link between hyperglycemia, oxidative stress, coagulopathy and inflammation and between these factors and the vascular damage. Various studies have showed the potential role of adhesion molecules in the pathogenesis of diabetic vasculopathy. They promote leukocyte recruitment, which is one of the initial steps in the genesis of atherosclerotic plaque. Adhesion molecules are also involved in the pathogenesis of diabetes mellitus type 1; sICAM-1 would have a particular immunomodulatory role in the process of destroying beta-cells and could be used as a subclinical marker of insulitis. Plasma levels of soluble adhesion molecules correlate with hyperglycemia, insulin resistance, dyslipidemia and obesity; they are associated with the development of nephropathy, retinopathy, myocardial infarction, stroke and obliterant peripheral arterial disease in diabetic type 1 and 2. Given the role of these molecules in endothelial dysfunction genesis and tissue damage associated with diabetes, they could constitute a therapeutic target for the prevention of genesis and progression of chronic complications of diabetic disease.
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PMID:[Adhesion molecules and diabetes mellitus]. 2054 49