Pericytes are cells of the extracellular matrix and surround all capillaries with their contractile projections. In one major function, they perform dilatation and constriction of capillaries because capillary endothelia lack muscle cells and rely on external control of their lumen. In addition, pericytes perform important functions in the proliferation of endothelial cells in the formation of new vessels (angiogenesis).
What is a pericyte?
Pericytes (pericytes) are part of the extracellular matrix, that is, part of the connective tissue. Characteristic of pericytes are their contractile star-shaped cell processes, which they use to surround capillaries so that they can dilate or constrict them as needed. Because smooth muscle cells are also integrated into the walls of arteries and veins, the (healthy) vessels can manage their own dilatation and constriction. The vessel walls of capillaries do not contain smooth muscle cells, so they rely on pericytes for support. Most pericytes originate from the mesenchyme. Some authors argue that they may also develop by transformation of endothelial cells. Conversely, it is also thought that pericytes can also develop into other mesenchymal cells such as fibroblasts, osteoblasts, chondrocytes, and others. Because pericytes are directly integrated into the basement membrane of capillaries, they are also classified as vascular wall cells. Pericytes are present in all tissues traversed by blood vessels. Strikingly, they are found in particular abundance in the central nervous system and are associated with the maintenance of the blood–brain barrier.
Anatomy and structure
Morphologically, pericytes do not have a uniform shape. The external shape of the cells adapts to their particular function. All pericytes have a nucleus and a relatively small amount of cytoplasm. The nucleus changes depending on the tasks that the pericytes perform. In tissue that is regenerating or in the growth phase, the nuclei assume a spherical shape and are euchromatically disrupted. In differentiated tissue, the nuclei appear heterochromatic and flattened. The cytoplasm contains mitochondria for energy supply, myofilaments, and glycogen particles. The myofilaments are filamentous protein structures that provide contractility to the multiple cell processes of pericytes in a complex interplay between myosin and actin. The connection between the processes and the endothelium of the capillaries occurs via so-called tight junctions, which also transmit the contractile forces to the endothelium of the capillaries. The cytoplasm also contains multivesicular inclusions and plasmalemmal vesicles, which are otherwise found only as vesicular inclusions in the cytoplasm of endothelial cells. The multiple cell processes that enclose the capillaries often have club-shaped extensions at their ends. Some authors argue that these extensions serve to close or open the gaps in the endothelium of capillaries as needed to control the exchange of substances that occurs across the gaps (holes). This assumption is compatible with the accumulation of pericytes in the CNS. In the CNS, pericytes surround capillaries with almost no gaps, so that they can almost completely block the exchange of substances between the capillaries and the surrounding nervous tissue when needed. Pericytes have all the necessary “tools” to be able to synthesize proteins.
Function and tasks
Pericytes perform a number of different known major tasks and functions. However, not all functions of pericytes are yet sufficiently known, and further research is needed. One of the undisputed major roles is the regulation of vascular tone in the capillaries that they surround. The pericyte processes can contract or dilate and transmit the contracting or dilating effect to the capillaries via tight junctions. Pericytes also perform important functions in maintaining the blood–brain barrier in the CNS. Extensions on their projections make it possible to almost completely close the fenestrated (with gaps or holes) endothelia of the capillaries, through which the exchange with macromolecules takes place. This results in a very selective exchange of substances between the CNS and the blood capillaries.This is to ensure that toxic substances, pathogenic germs or certain hormones cannot penetrate the nervous tissue of the CNS. Another task of pericytes is to support angiogenesis, the formation of new blood vessels in new or growing tissue. The cell processes of pericytes provide physical stability to the new blood vessels and synthesize second messengers that stimulate angiogenesis. The role of pericytes in inflammation caused by infection or blunt (sterile) injury has not been adequately explored.
Diseases
Because of the nearly ubiquitous distribution of pericytes in the body and their key role in maintaining capillary blood and lymph flow, dysfunction of pericytes plays a role in many diseases and symptoms. Often, symptoms are triggered by an excess of pericytes in a particular tissue section or by their deficiency. In both cases, there are disturbances in capillary blood pressure and metabolic exchange. In the early stage of diabetic retinopathy, there is an increasing loss of pericytes in the area of the retina, so that the retaining function of the pericytes for the capillaries is lost and there are often microaneurisms on the retina with corresponding visual impairments. The loss of pericytes in the CNS of elderly people can lead to a functional impairment of the blood-brain barrier and to an unintended exchange of substances, triggering neurodegenerative inflammations and leading to increased cell death (apoptosis) of neurons. After strokes, it was observed that capillaries in the CNS area were constricted by pericytes and then died, further impairing the blood-brain barrier and leading to increased neuronal cell death.
