Tag: TFIIH

Pericytes are pluripotent cells that can be found in the vascular

Pericytes are pluripotent cells that can be found in the vascular wall of both microvessels and large arteries and veins. cells with atherogenic low-density lipoprotein. In this review we will discuss the application of P7C3-A20 distributor cellular models for studying atherosclerosis and P7C3-A20 distributor provide several examples of successful application of these models to drug research. 1. Introduction Mural cells isolated from your human vascular wall represent a heterogeneous populace, made up of pericytes or pericyte-like cells together with other cell types. Pericytes, or perivascular cells, are characterized by branched morphology and the formation of numerous contacts between each other and with endothelial cells (ECs). Pericytes are embedded into the basement membrane of the vascular wall and wrap round the ECs [1, 2]. They are responsible for microvascular growth and branching [3]. Pericytes can be found invasa vasorummicrovessels that provide alimentation of wall tissue of large blood vessels [4, 5]. Furthermore, presence of stellate pericyte-like cells in the intima of large arteries and veins has been reported in a series of studies [6, 7]. Pericytes are pluripotent cells and can differentiate to other cell types, such as myofibroblasts, osteoblasts, and adipocytes. It is possible that pericytes possess regenerative properties in healthy tissue participating in vascular remodelling and vascular injury repair [8]. At the same time, pericytes may play a central role in the development of vascular pathologies. The discovery of pericytes and pericyte-like cells in the large arteries highlights the possibility of their involvement in the atherosclerotic process. Indeed, recent studies exhibited that pericytes play important functions in atherogenesis, accumulating lipids, promoting the atherosclerotic plaque growth and vascularization, participating in vascular remodelling, calcification, and thrombosis (examined in [6]). It is also likely that these pluripotent cells may express proinflammatory molecules and thus orchestrate the local inflammation, which plays an important role in atherosclerosis. Pericytes and pericyte-like cells can be extracted from postmortem samples of human aortic tissue and utilized for studying atherogenesis, as well as screening various substances with potential antiatherosclerotic activity. Such cellular models are highly relevant and therefore very P7C3-A20 distributor encouraging for atherosclerosis research and drug development. 2. Cellular Structure of Human Arterial Intima The human arterial wall consists of several unique layers (Physique 1). Immediately below the endothelial lining of the artery lies the proteoglycan-rich layer, which is also known as elastic-hyperelastic or connective-tissue layer. It contains connective-tissue fibres that have no unique orientation and a heterogeneous cell populace. Proteoglycan-rich layer is usually separated from more distal layers of the arterial wall by the internal limiting membrane. Beyond the internal limiting membrane lies the muscular-elastic layer, which consists of longitudinally oriented elongated cells and elastic fibres. The layers differ from each other both by the cell populace and by the composition of glycosaminoglycans [6]. Open in a separate window Physique 1 Schematic representation of the proteoglycan-rich layer of human aortic intima. Stellate macrovascular pericytes form a three-dimensional cellular network in the subendothelial layer of intima forming contacts with each other and other cell types. Cellular composition of the TFIIH subendothelial proteoglycan-rich layer is usually heterogeneous, as the layer contains both resident cells and monocytes/macrophages and lymphocytes that infiltrate into the intima from the bloodstream [9]. However, in healthy human aortic intima, cells of haematogenous origin represent the minority, accounting for as little as 5% of the total cell populace [6]. Among the resident cells, vascular easy muscle cells, characterized by on fibroblasts and astrocytes [20]. Therefore, the identification of pericytes is best performed using a combination of known markers. For example, an immunocytochemical analysis of pericytes could be performed using a combination of vasa vasorumcan also contribute to the atherosclerotic plaque growth by orchestrating neovascularization of growing plaques [6]. 5. Cellular Models Based on Primary Culture of Subendothelial Cells Current therapy of atherosclerosis is largely based on the use of lipid-lowering drugs, such as statins [33, 34]. However, no therapy with direct antiatherosclerotic activity has been developed so far. Screening for therapeutic agents allowing the reduction of lipid accumulation in the arterial wall and atherosclerotic plaque growth requires development of adequate disease models. Given that subendothelial cells are playing a prominent role at all stages of the pathologic process including the initial lesion formation, primary culture of these cells appears to be promising for establishing such models. Cellular tests based on these cultures can be used for studying the early stages of atherogenesis and blood serum atherogenicity. Such assessments are readily available and suitable for testing of large panels of substances prior to preclinical and clinical.