Pericyte

Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries and venules throughout the body. Pericytes are embedded in basement membrane, where they communicate with endothelial cells of the body's smallest blood vessels by means of both direct physical contact and paracrine signaling. Pericytes help to maintain homeostatic and hemostatic functions in the brain and also sustain the blood–brain barrier. These cells are also a key component of the neurovascular unit, which includes endothelial cells, astrocytes, and neurons. Pericytes regulate capillary blood flow, the clearance and phagocytosis of cellular debris, and the permeability of the blood–brain barrier. Pericytes stabilize and monitor the maturation of endothelial cells by means of direct communication between the cell membrane as well as through paracrine signaling. A deficiency of pericytes in the central nervous system can cause the blood–brain barrier to break down. Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries and venules throughout the body. Pericytes are embedded in basement membrane, where they communicate with endothelial cells of the body's smallest blood vessels by means of both direct physical contact and paracrine signaling. Pericytes help to maintain homeostatic and hemostatic functions in the brain and also sustain the blood–brain barrier. These cells are also a key component of the neurovascular unit, which includes endothelial cells, astrocytes, and neurons. Pericytes regulate capillary blood flow, the clearance and phagocytosis of cellular debris, and the permeability of the blood–brain barrier. Pericytes stabilize and monitor the maturation of endothelial cells by means of direct communication between the cell membrane as well as through paracrine signaling. A deficiency of pericytes in the central nervous system can cause the blood–brain barrier to break down. In the central nervous system, pericytes wrap around the endothelial cells that line the inside of the capillary. These two types of cells can be easily distinguished from one another based on the presence of the prominent round nucleus of the pericyte compared to the flat elongated nucleus of the endothelial cells. Pericytes also project finger-like extensions that wrap around the capillary wall, allowing the cells to regulate capillary blood flow. Both pericytes and endothelial cells share a basement membrane where a variety of intercellular connections are made. Many types of integrin molecules facilitate communication between pericytes and endothelial cells separated by the basement membrane. Pericytes can also form direct connections with neighboring cells by forming peg and socket arrangements in which parts of the cells interlock, similar to the gears of a clock. At these interlocking sites, gap junctions can be formed, which allow the pericytes and neighboring cells to exchange ions and other small molecules. Important molecules in these intercellular connections include N-cadherin, fibronectin, connexin and various integrins. In some regions of the basement membrane, adhesion plaques composed of fibronectin can be found. These plaques facilitate the connection of the basement membrane to the cytoskeletal structure composed of actin, and the plasma membrane of the pericytes and endothelial cells. Pericytes in the skeletal striated muscle are of two distinct populations, each with its own role. The first pericyte subtype (Type-1) can differentiate into fat cells while the other (Type-2) into muscle cells. Type-1 characterized by negative expression for nestin (PDGFRβ+CD146+Nes-) and type-2 characterized by positive expression for nestin (PDGFRβ+CD146+Nes+). While both types are able to proliferate in response to glycerol or BaCl2-induced injury, type-1 pericytes give rise to adipogenic cells only in response to glycerol injection and type-2 become myogenic in response to both types of injury. The extent to which type-1 pericytes participate in fat accumulation is not known. Pericytes are also associated with allowing endothelial cells to differentiate, multiply, form vascular branches (angiogenesis), survive apoptotic signals and travel throughout the body. Certain pericytes, known as microvascular pericytes, develop around the walls of capillaries and help to serve this function. Microvascular pericytes may not be contractile cells because they lack alpha-actin isoforms; structures that are common amongst other contractile cells. These cells communicate with endothelial cells via gap junctions and in turn cause endothelial cells to proliferate or be selectively inhibited. If this process did not occur, hyperplasia and abnormal vascular morphogenesis could occur. These types of pericyte can also phagocytose exogenous proteins. This suggests that the cell type might have been derived from microglia. A lineage relationship to other cell types has been proposed, including smooth muscle cells, neural cells, NG2 glia, muscle fibers, adipocytes, as well as fibroblasts and other mesenchymal stem cells. However, whether these cells differentiate into each other is an outstanding question in the field. Pericytes' regenerative capacity is affected by aging. Such versatility is conducive because they actively remodel blood vessels throughout the body and can thereby blend homogeneously with the local tissue environment. Aside from creating and remodeling blood vessels in a viable fashion, pericytes have been found to protect endothelial cells from death via apoptosis or cytotoxic elements. It has been studied in vivo that pericytes release a hormone known as pericytic aminopeptidase N/pAPN that may help to promote angiogenesis. When this hormone was mixed with cerebral endothelial cells as well as astrocytes, the pericytes grouped into structures that resembled capillaries. Furthermore, if experimental group contained all of the following with the exception of pericytes, the endothelial cells would undergo apoptosis. That being said, it was concluded that pericytes must be present to assure the proper function of endothelial cells and astrocytes must be present to assure that both remain in contact. If not, then proper angiogenesis cannot occur. In addition, it has been found that pericytes contribute to the survival of endothelial cells because they secrete the protein Bcl-w during cellular crosstalk. Bcl-w is an instrumental protein in the pathway that enforces VEGF-A expression and discourages apoptosis. Although there is some speculation as to why VEGF is directly responsible for preventing apoptosis, it is believed to be responsible for modulating apoptotic signal transduction pathways and inhibiting activation of apoptosis-inducing enzymes. Two biochemical mechanisms utilized by VEGF to accomplish such would be phosphorylation of extracellular regulatory kinase 1 (ERK-1), which sustains cell survival over time, and inhibition of stress-activated protein kinase/c-jun-NH2 kinase, which also promotes apoptosis. Pericytes play a crucial role in the formation and functionality of the selectively permeable space between the circulatory system and central nervous system. This space is known as the blood–brain barrier. This barrier is composed of endothelial cells and assures the protection and functionality of the brain and central nervous system. Although it had been theorized that astrocytes were crucial to the postnatal formation of this barrier, it has been found that pericytes are now largely responsible for this role. Pericytes are responsible for tight junction formation and vesicle trafficking amongst endothelial cells. Furthermore, they allow the formation of the blood–brain barrier by inhibiting the effects of CNS immune cells (which can damage the formation of the barrier) and by reducing the expression of molecules that increase vascular permeability.