User:LewisCS13/pericyte

Definition

Pericytes are connective tissue cells (also known as "Rouget," "mural," and "vascular smoothe muscle cells") that play an important role in microvessel support and endothelium proliferation.

Structure and Components

Pericytes have a basement membrane shared with endothelial cells. This membrane contains invagenated "peg and socket" junctions rich in tight and gap junctions. Pericytes also express different markers depending on the location and function of the cell that can help to identify the pericyte.

Function

Blood Brain Barrier

Pericytes play a crucial role in the formation and functionality of the selective permeable space between the circulatory and central nervous system that is 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 be theorized that astrocytes were largely important in 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 .

Aside from blood brain barrier formation, pericytes also play an active role in its functionality by controlling the flow within blood vessels and between blood vessels and the brain. They are contractile cells so they can open or close a given amount to allow (or disallow) certain sized particles to flow through the vessel. Such regulation of blood flow is beneficial to neuronal function because it protects the brain from undesired particles. Without the presence of pericytes, a process known as transcytosis may occur within the blood brain barrier. This essentially means that there is little to no regulation by the barrier and particles of varying sizes, including large plasma proteins, can easily enter the brain . This passage of particles can be adverse to the brain because many of these particles can be toxic. Thus, pericytes play a critical role in assuring that harmful chemicals do not enter the brain and disrupt neurological function. Pericyte functionality (or disfunctionality) is also theorized to contribute to neurodegenerative diseases such as Alzheimer’s, Parkinson’s and ALS. Furthermore, the elasticity of pericyte is beneficial because they can expand to reduce inflammation and allow harmful substances to diffuse out of the brain .

These cells also play a key role in increasing microcirculation and reducing the effects or brain aging. In a study involving adult pericyte-deficient mice, the absence of pericytes in the brain has been found to lead to vascular damage from loss of microcirculation and cerebral blood flow. Such blood flow is imperative to mediate the effects caused by stress, hypoxia and several other conditions which may alter homeostasis. In addition, when pericytes are not present, the blood brain barrier does not degrade certain neurotoxic and vasculotoxic serum proteins which thus bolsters degenerative changes. Such changes include inflammation as well as learning and memory impairment .

Angiogenesis and the Survival of Epithelial Cells

Pericytes are also associated with the allowing Endothelial Cells to differentiate, multiply, form vascular branches, survive apoptotic symbols 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 a-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 pericytes can also phagocytose exogenous proteins. This suggests that the cell type might have been derived from microglia .

It is also important to note that pericytes maintain plasticity and thus can differentiate into various other cell types including, smooth muscle cell as well as fibroblasts and other mesenchymal cells. Such versatility is conducive because they actively remodel blood vessels throughout the body and must be homogenous with the surroundings .

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 and 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, than 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 discourages apoptosis. That being said, pericytes also promotes protection of endothelial cells against several cytotoxic elements

Clinical significance

Hypertension

Pericytes and their smooth muscle components may play a role in hypertension.

Hemangiopericytoma

A rare and possibly malignant vascular tumor, this soft-tissue sarcoma is caused by the abnormal growth of pericytes.

Diabetic retinopathy

This disease involves damage to the eye's retina, and we will explore pericytes' role in its development.

Alzheimer's Disease

Pericytes may play a role in this disease, as they can be found in excess in the blood vessels of the brain for afflicted patients.

Multiple Sclerosis

An autoimmune disease affecting the central nervous system.

Recent Studies

Pericytes and Kidney Fibrosis

Pericytes play a pivotal role in fibrosis of kidney cell.

Endothelial and Pericyte Interactions

Abnormal interactions between the endothelial cells and the pericytes are connected to human pathology.

Scarring

Subtypes of pericytes provide a major contribution to the core of glial scars after injury to the central nervous system

Notes

1. Daneman, Richard et al. (2010) Pericytes are required for blood–brain barrier integrity during embryogenesis. "nature" 468, 562-566

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5. Pericyte, Astrocyte and Basal Lamina Association with the Blood Brain Barrier (BBB)

6. Gerhardt H, Betsholtz C.(2003) Endothelial-pericyte interactions in angiogenesis. "Cell Tissue Res." 314(1), 15-23

7. Ramsauer, Markus et. al. (2002) Angiogenesis of the blood-brain barrier in vitro and the function of cerebral pericytes "The FASEB Journal" 10.1096/fj.01-0814fje

8. Franco, Marcela et al. (2011) Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression "Blood"

Armulik A & Abramsson A & Betsholtz C (2005). Edothelial/Pericyte interactions. "Circulation Research", 97, 512-523.

Goritz C (2011). A pericyte origin of spinal chord scar tissue. "Science", 333, 238-242.

Kida Y & Duffield JS (2011). Pivotal role of pericytes in kidney fibrosis. "Clinical and Experimental Pharmacology & Physiology", 38(7), 417-423.