Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycosaminoglycans (GAGs) have been implicated in the pathogenesis of sclerotic vascular disease. The localization of GAGs in the rat aorta was examined by two different ultrastructural cytochemical approaches. These procedures are believed to demonstrate 1) anionic sites, with fixatives that contain either toluidine blue or ruthenium red, both cationic dyes, and 2) polysaccharides, proteoglycans, and glycoproteins, with an osmium--ferrocyanide mixture that binds to vicinal diols. Both procedures stain a network of insoluble, 2--8-nm filaments that bridge collagen fibers, elastin, basement membranes, and plasma membranes. These structures resist digestion with chondroitinase ABC and appear to be identical to the filaments that have previously been demonstrated with ruthenium red. Focal 6--12-nm densities are present where filaments intersect. However, the large granules that are made visible with ruthenium red are not seen in toluidine blue or osmium--ferrocyanide preparations. A soluble and relatively amorphous component surrounds the tightly packed bundles of collagen in the media and is preserved and stained by toluidine blue and osmium--ferrocyanide mixtures.
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PMID:Glycosaminoglycans in the rat aorta. Ultrastructural localization with toluidine blue O and osmium--ferrocyanide procedure. 617 40

Hyaluronan (HA) accumulates in vascular disease but its functional role is not fully understood. To investigate the impact of HA enriched extracellular matrices (ECM) on cell phenotype, arterial smooth muscle cells (ASMCs) were transduced with retroviral constructs (LXSN) encoding murine has-1, has-2, and has-3. HA synthesis was significantly elevated in has transduced ASMCs. Metabolically labeled HA from has-1 and has-2 transduced cells was present mostly in high molecular weight (HWA) fractions (2-10x10(6) Da), whereas HA produced by has-3 and control cells was present in lower molecular weight fractions (approximately 2x10(6) Da). Both has-1 and has-3 transduced ASMCs accumulated more pericellular HA than has-2 transduced ASMCs. All has transduced ASMCs had attenuated growth and migration rates, and a decreased detachment response. Affinity histochemistry revealed that has-1 transduced ASMCs accumulated the greatest amount of HA containing ECM than the other transduced ASMCs. This ECM was hyaluronidase sensitive and bound a significantly greater number of monocytes than the ECM generated by has-2 or has-3 transduced ASMCs. Confocal microscopy showed CD44 positive monocytes bound to hyaluronidase sensitive ECM in has-1 transduced ASMCs. These data implicate specific has isoforms in the formation of HA enriched pro-inflammatory ECMs.
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PMID:Overexpression of hyaluronan synthases alters vascular smooth muscle cell phenotype and promotes monocyte adhesion. 1611 Apr 80

Vascular integrity or the maintenance of blood vessel continuity is a fundamental process regulated, in part, by the endothelial glycocalyx and cell-cell junctions. Defects in endothelial barrier function are an initiating factor in several disease processes including atherosclerosis, ischemia/reperfusion, tumor angiogenesis, cancer metastasis, diabetes, sepsis and acute lung injury. The glycosaminoglycan, hyaluronan (HA), maintains vascular integrity through endothelial glycocalyx modulation, caveolin-enriched microdomain regulation and interaction with endothelial HA binding proteins. Certain disease states increase hyaluronidase activity and reactive oxygen species (ROS) generation which break down high molecular weight HA to low molecular weight fragments causing damage to the endothelial glycocalyx. Further, these HA fragments can activate specific HA binding proteins upregulated in vascular disease to promote actin cytoskeletal reorganization and inhibition of endothelial cell-cell contacts. This review focuses on the crucial role of HA in vascular integrity and how HA degradation promotes vascular barrier disruption.
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PMID:Hyaluronan regulation of vascular integrity. 2225 99

Deciphering the extracellular signals that regulate SMC differentiation from stem cells is vital to further our understanding of the pathogenesis of vascular disease and for development of cell-based therapies and tissue engineering. Hyaluronan (HA) has emerged as an important component of the stem cell niche, however its role during stem cell differentiation is a complicated and inadequately defined process. This study aimed to investigate the role of HA in embryonic stem cell (ESC) differentiation toward a SMC lineage. ESCs were seeded on collagen-IV in differentiation medium to generate ESC-derived SMCs (esSMCs). Differentiation coincided with increased HA synthase (HAS) 2 expression, accumulation of extracellular HA and its assembly into pericellular matrices. Inhibition of HA synthesis by 4-methylumbelliferone (4MU), removal of the HA coat by hyaluronidase (HYAL) or HAS2 knockdown led to abrogation of SMC gene expression. HA activates ERK1/2 and suppresses EGFR signaling pathways via its principle receptor, CD44. EGFR inactivation coincided with increased binding to CD44, which was further augmented by addition of high molecular weight (HMW)-HA either exogenously or via HAS2 overexpression through adenoviral gene transfer. HMW-HA-stimulated esSMCs displayed a functional role in vascular tissue engineering ex vivo, vasculogenesis in a matrigel plug model and SMC accumulation in neointimal lesions of vein grafts in mice. These findings demonstrate that HAS2-induced HA synthesis and organization drives ESC-SMC differentiation. Thus, remodeling of the HA microenvironment is a critical step in directing stem cell differentiation toward a vascular lineage, highlighting HA as a potential target for treatment of vascular diseases. Stem Cells 2016;34:1225-1238.
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PMID:Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage. 2686 48