Pericytes, a kind of pluripotent cell, embedded in the vascular basement, have recently come into focus as regulators of irrigation flow and permeability of microcirculation. It is similar to smooth muscle cells expressing several kinds of contractile proteins which are responsible for its contractility. They are highly present in the CNS compared to the vasculature of lungs, and muscle. Pericytes ensheathe the endothelial wall of microcirculation and are encapsulated within the basement membrane. These pericytes are connected to the endothelial cells (ECs) through pegs, sockets and adhesion plaques. Although, pericytes are present in the pre-capillaries, capillaries, post-capillary venules, venules and arterioles, but, the coverage of pericyte is more extensive in the post-capillary venules. According to the morphology and location, they may be different. For example, pre and post-capillary pericytes are large with thick and star shaped processes and are rich in alpha-smooth muscle actin (α-SMA) and mid-capillary pericytes are sparse with slender and spindle shaped cytoplasmic processes and do not express α-SMA expression. Pericytes express some markers, which helps their identification, including membrane bound markers such as PDGFR-β NG-2, CD13, CD90, CD105 and cytosolic markers such as α-SMA, non-muscle myosin, desmin, nestin, vimentin etc. Recently, a new cytosolic marker, RGS5 is identified and believed to be specific for pericyte identification.
Pericytes play an important role in endothelial barrier development and maintenance of integrity and contribute to forming functional neurovascular units, by having contact with microglia, neurons, ECs, and astrocyte end-feet. They could secrete multifunctional cytokine, TGF-β to support blood-brain-barrier (BBB) integrity through stabilizing the structure of actin filaments in ECs and pericyte derived Ang-1 can promote the tight junction protein expression in ECs. Therefore, loss of pericyte could lead to damage in the BBB in vivo.
Pericyte may respond to the vasoconstrictors like Ang-II, serotonin, vasodilators like NO. Its structural marker protein such as α-SMA, vimentin etc, which are associated with constriction, contribute to the actin filament bundles located near the EC. Studies have proved that, hypoxic condition triggers pericyte relaxation and hyperoxic condition induces contraction. They also play a pivotal role in forming and stabilizing the angiogenesis and could regulate endothelial cell migration, proliferation and differentiation. Furthermore, it releases VEGF and promotes endothelial cell maturation.
Brain pericytes are found to express some stem cell markers such as CD44, CD73, CD90, CD105 and show similar characteristics with mesenchymal stem cells (MSCs). Therefore, it can regenerate itself and be able to differentiate into neurons, oligodendrocytes, and astrocytes. It may participate in various diseases in the CNS and generate new drug targets for therapies. Moreover, it may intake small molecules or soluble molecules in blood or brain parenchyma by phagocytosis, endocytosis, and pinocytosis. In the physiological condition, they express adhesion molecules at a lower level. However, in pathological conditions, they express TNF-α, IFN-ꙋ, MHC-II and present them to T lymphocyte.
The loss of pericytes is found to be associated with the breakdown of the endothelial junction in pathological angiogenesis when pericyte coverage is lost from the retinal capillaries and results in the breakdown of ECs proliferation, thickened basal membrane and retinal barrier, which later on can lead to severe hemorrhage and retinal detachment. It has also been found that pericytes are highly sensitive to inflammatory signalling and may drive leukocytes to the inflammatory site. It recruits macrophages and enhances endothelial cell interactions. When stimulated with TNF- or LPS, pericytes release large amounts of pro-inflammatory molecules, anti-inflammatory molecules, chemokines, and cytokines. Furthermore, loss of pericytes in the cardiac microvascular leads to coronary flow reserve impairment, interstitial permeability increase, and cardiac microvascular dysfunction.
Reference:
Zhang, Zi-Sen; Zhou, He-Nan; He, Shuang-Shuang; Xue, Ming-Ying; Li, Tao; Liu, Liang-Ming (2020). Research advances in pericyte function and their roles in diseases. Chinese Journal of Traumatology, (), S1008127520300766–. doi:10.1016/j.cjtee.2020.02.006
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