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)

Adhesion molecules and chemoattractants are thought to play a critical role in the homing of leukocytes to sites of vascular lesions. Apo-E deficiency in mice creates an atherosclerotic model that mimics vascular lesions in man. Little is known on the effect of Apo-E deficiency on expression of adhesion molecules in the hearts of these animals. In this study, male C57BL6 and Apo-E deficient mice were fed a chow diet over periods of time (0 to 20 weeks). The transcription levels of major adhesion molecules (ICAM-1, PECAM-1), present in the heart, were followed by northern blots. Immunohistochemistry was used to localize these adhesion molecules in the heart. Results show a significant increase in gene transcription levels of ICAM-1 and PECAM-1 in Apo-E animals, but not wild type, at 16 and 20 weeks of chow diet. Such increase in levels of transcription was not observed in younger Apo-E and C57BL6 animals (0, 6 weeks of diet). ICAM-1 and PECAM-1 were strongly expressed in the endocardium and heart microvessels. In contrast, VCAM-1 was poorly stained, with only an occasional expression on the endocardium and arterioles. Enhanced gene expression levels of heart ICAM-1 and PECAM-1 observed in Apo-E deficient mice, but not in control animals, appears to induce the initial stages of an inflammatory reaction. Such observations, not previously reported, may induce heart vascular remodeling.
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PMID:Increased ICAM-1 and PECAM-1 transcription levels in the heart of Apo-E deficient mice in comparison to wild type (C57BL6). 1137 87

Macrophage-derived apoE in the vessel wall has important effects on atherogenesis in vivo, making it important to understand factors that regulate its expression. Vessel wall macrophages are embedded in an extracellular matrix produced largely by arterial smooth muscle cells and endothelial cells. In this series of studies, we evaluated the influence of extracellular matrix on macrophage apoE expression. Subendothelial matrix, fibronectin, or collagen I stimulated macrophage apoE gene expression and apoE synthesis. Adhesion of macrophages to a polylysine substrate had no effect. An increase in apoE synthesis after plating on fibronectin could be observed by 2 h and was inhibited by blocking antibodies to the alpha(5)beta(1) integrin receptor for fibronectin. Fibronectin also regulated the post-translational processing of newly synthesized macrophage apoE by inhibiting its degradation. The increment in apoE resulting from suppressed degradation was retained in the cell-fibronectin monolayer in a pool that was resistant to release by exogenous high density lipoprotein subfraction 3. These observations establish a new pathway for the regulation of macrophage apoE expression in the vessel wall. The composition of the extracellular matrix changes after vessel wall injury and in response to locally produced cytokines and growth factors. The evolving composition of this matrix will, therefore, be important for regulating apoE expression and processing by vessel wall macrophages.
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PMID:Regulation of macrophage ApoE expression and processing by extracellular matrix. 1203 16

Adhesion molecules have been implicated in the development and progression of cardiovascular disease, which is highly prevalent in people with diabetes. Adhesion molecules can mediate adhesion of leukocytes to the endothelium. Furthermore, P-selectin expressed on platelets is able to mediate the adhesion of leukocytes to platelets. In this study, we examine the in-vivo and in-vitro effects of rosiglitazone with particular emphasis on three important adhesion molecules (VCAM-1, ICAM-1 and P-selectin). In the aorta of STZ-diabetic apolipoprotein E-deficient (apoE KO) mice, rosiglitazone significantly reduced both total and arch plaque area. The mechanism for this appeared to be reduced macrophage infiltration into the atherosclerotic plaque which was also associated with reduced mRNA levels for VCAM-1, ICAM-1, MCP-1 and P-selectin in the aorta. In-vitro studies revealed reduced cell adhesion of monocytic cells (THP-1) to fibrinogen and endothelial cells (HUVEC) after incubation with rosiglitazone. Furthermore, the reduction in leukocyte adhesion also correlated with significant reductions in mRNA levels for VCAM-1, ICAM-1 and P-selectin indicating that reduced macrophage infiltration in atherosclerotic plaques may occur as a result of a direct effect of rosiglitazone on adhesion molecules in both monocytes and endothelial cells. Thus, we have shown that rosiglitazone appears to have direct anti-atherosclerotic effects in an animal model of diabetes-associated atherosclerosis which are at least partly due to effects on VCAM-1, ICAM-1, MCP-1 and P-selectin expression which leads to decreased leukocyte adhesion and macrophage infiltration.
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PMID:Reduced plaque formation induced by rosiglitazone in an STZ-diabetes mouse model of atherosclerosis is associated with downregulation of adhesion molecules. 1809 96

Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.
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PMID:A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A. 2030 57

Inflammation plays a fundamental role in many chronic diseases, including atherosclerosis associated cardiovascular disease. Adhesion of immune cells plays a critical role in the inflammatory response and indeed the pathophysiology of inflammatory related diseases. P-selectin is an inflammatory adhesion molecule, enabling the recruitment of leukocytes to the endothelium and to activated platelets involved with the growing thrombus. P-selectin is critical in the progression of atherosclerosis as evidenced by knockout animal models where P-selectin knockout mice crossed with apoE deficient mice exhibit significantly reduced atherosclerosis and leukocyte recruitment in the plaque. A soluble form of P-selectin also exists, which may have pro-atherogenic and pro-thrombotic effects. Thus targeting of P-selectin remains a strong clinical candidate for developing novel therapeutic strategies in inflammatory diseases. This review will discuss the role of P-selectin and describe the function of P-selectin antagonists as clinical targets.
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PMID:P-selectin antagonism in inflammatory disease. 2124 96