Pericytes are highly specialized, microscopic cells that support the body’s vast network of microvessels. They are positioned on the outer surface of capillaries, the smallest blood vessels where oxygen and nutrient exchange occurs. Pericytes are integral to the vascular system, contributing to the health and function of blood flow in every organ and tissue. Their widespread presence establishes them as important components of microcirculation.
Fundamental Identity and Location
Pericytes are classified as mural cells, meaning they reside within the walls of blood vessels, specifically the capillaries and post-capillary venules. They are situated on the abluminal surface of the vessel, facing away from the blood flow. They share a common basement membrane with the inner endothelial cells, allowing for direct cell-to-cell communication essential for vascular signaling.
The physical structure of a pericyte is distinctive, often described as stellate or spider-like, with a central cell body and long, thin cytoplasmic processes. These processes wrap around the capillary tube, spanning the surface of several endothelial cells. This association is reinforced by contractile proteins, such as actin and myosin, which gives pericytes the ability to generate force.
This contractile machinery allows pericytes to physically alter the diameter of the capillary. The density of pericytes varies significantly by organ, with the highest concentration found in the capillaries of the central nervous system. Their location and structure enable their dynamic functions, particularly the regulation of blood flow and vessel integrity.
Primary Function: Vascular Stability and Blood Flow Regulation
A primary role of pericytes outside of the brain is to maintain the structural stability and integrity of the microvessels in peripheral circulation, such as in the skin, muscles, and internal organs. During the formation of new blood vessels, a process known as angiogenesis, pericytes are recruited to nascent endothelial tubes to provide physical and biochemical stabilization. This recruitment, often mediated by the Platelet-Derived Growth Factor-Beta (PDGF-\(\beta\)) system, is necessary for the vessels to mature and function correctly.
Pericytes also control vascular permeability by influencing the tight junctions between adjacent endothelial cells. Communication between pericytes and endothelial cells, often involving molecules like Transforming Growth Factor-Beta (TGF-\(\beta\)) and Angiopoietin-1, regulates the passage of plasma fluids and molecules from the blood into the surrounding tissue. A stable pericyte-endothelial association helps prevent vascular leakage, which is crucial for maintaining tissue homeostasis.
Pericytes act as local regulators of blood flow within the capillary beds. Their contractile properties allow them to constrict or relax the capillary lumen, adjusting the local blood supply in response to tissue needs. This micro-level regulation ensures that active areas, such as muscle tissue, receive appropriate amounts of oxygen and nutrients. This function is important in tissues where dedicated smooth muscle cells are absent on the smallest vessels.
Specialized Role in the Central Nervous System
The function of pericytes is uniquely amplified within the brain and spinal cord, where they are integral components of the Neurovascular Unit (NVU). The NVU is a complex cellular network that includes neurons, astrocytes, endothelial cells, and pericytes, managing the brain’s blood supply and microenvironment. Pericytes are far more abundant in the brain’s capillaries compared to other organs, highlighting their specialized importance.
Pericytes are essential for the formation and maintenance of the Blood-Brain Barrier (BBB), which acts as a highly selective boundary between the circulating blood and the brain tissue. They signal to the endothelial cells to induce and maintain the tight junctions that restrict the passage of substances. A breakdown in pericyte coverage is directly correlated with increased BBB permeability, allowing potentially harmful toxins and pathogens to enter the neural tissue.
Within the NVU, pericytes are responsible for coupling neuronal activity with changes in local blood flow, a mechanism known as neurovascular coupling. When neurons become active, they signal the pericytes to relax, leading to a rapid increase in capillary diameter to boost oxygen and glucose delivery. Conversely, pericyte contraction can reduce blood flow, managing resource distribution throughout the brain parenchyma.
Brain pericytes play a role in immunological surveillance and waste clearance. They are involved in clearing toxic metabolic byproducts, such as the amyloid-beta (\(\text{A}\beta\)) peptide that accumulates in Alzheimer’s Disease. Their proper functioning is directly linked to the protective environment of the central nervous system.
Pericytes and Disease States
When pericytes become dysfunctional or are lost, a wide range of human pathologies can result from the destabilization of the microvasculature. In neurodegenerative conditions like Alzheimer’s Disease, pericyte loss contributes to the breakdown of the Blood-Brain Barrier. This loss impairs the brain’s ability to clear \(\text{A}\beta\), accelerating the accumulation of toxic plaques and contributing to cognitive decline.
In acute events such as stroke, pericyte damage can exacerbate the outcome by leading to hemorrhagic transformation, where compromised vessel walls leak blood into the brain tissue. The loss of pericyte integrity causes microvessels to become fragile and prone to rupture, complicating recovery. Pericyte damage is also a feature of diabetic retinopathy, where their loss from retinal capillaries leads to microaneurysm formation and vascular leakage, a primary cause of vision impairment.
Pericytes also possess mesenchymal stem cell-like properties, allowing them to transform into other cell types under certain pathological conditions. Following tissue injury in organs like the kidney or liver, pericytes can undergo a phenotypic shift into myofibroblasts, which are cells that produce large amounts of extracellular matrix proteins. This transformation is a major contributor to organ scarring and fibrosis, leading to conditions like chronic kidney disease or liver cirrhosis.
The role of pericytes in cancer is complex, as they are involved in both promoting and inhibiting tumor growth. They participate in tumor angiogenesis, providing structure to the new blood vessels that feed the tumor mass. However, pericytes can also stabilize the tumor vasculature, which paradoxically improves chemotherapy delivery. This dual nature makes pericytes an intriguing therapeutic target.