Pericytes are specialized cells that wrap around the body’s smallest blood vessels, known as capillaries and post-capillary venules. First identified in 1873, they are embedded within the vascular basement membrane, a thin layer of extracellular matrix that surrounds these vessels. This positioning allows for communication with the endothelial cells that form the inner lining of the blood vessels. Modern research has revealed them as dynamic and multifaceted support cells for the microvasculature whose roles vary between different organs.
Regulating Blood Flow and Vessel Stability
Pericytes are integral to the structural integrity and regulation of the microvasculature. They extend long projections that encircle the capillary wall, physically reinforcing the vessel structure. This association helps maintain the stability of blood vessels, preventing leakage and ensuring they can withstand the pressure of blood flow. Without adequate pericyte coverage, capillaries can become fragile, dilated, and prone to hemorrhaging.
Beyond providing structural support, pericytes possess contractile proteins similar to those in smooth muscle cells. This feature allows them to actively change the diameter of the capillaries they surround. By contracting or relaxing, pericytes can control the amount of blood flowing through a specific capillary bed. This localized control responds to the metabolic needs of the surrounding tissue, such as inducing vessel dilation when more oxygen is required.
Angiogenesis and Tissue Repair
Pericytes have a role in the formation of new blood vessels, a process called angiogenesis. During both embryonic development and adult tissue repair, endothelial cells form new vascular sprouts, and pericytes are recruited to these structures. Their arrival is guided by signaling molecules, like Platelet-Derived Growth Factor-B (PDGF-B), released by endothelial cells. Pericytes then stabilize these new vessels, promoting their maturation into functional and non-leaky conduits.
This function is apparent during wound healing, where pericytes are among the first cells to invade newly vascularized tissue to help rebuild the blood supply. Furthermore, pericytes possess stem cell-like, or multipotent, characteristics. They have the capacity to differentiate into other cell types, such as fibroblasts, which create the connective tissue that forms scars. This ability allows them to contribute directly to the broader process of tissue reconstruction following injury.
Guarding the Blood-Brain Barrier
In the central nervous system (CNS), pericytes perform a specialized function in maintaining the blood-brain barrier (BBB). The BBB is a protective, highly selective border that prevents harmful substances in the blood from entering the brain. Pericytes are a component of this barrier, working with endothelial cells, astrocytes, and neurons in the neurovascular unit. The capillaries in the CNS have the highest degree of pericyte coverage found anywhere in the body.
Pericytes contribute to the formation and maintenance of the BBB’s integrity. They signal to endothelial cells to form and strengthen tight junctions, which are protein complexes that seal the space between adjacent endothelial cells. This action restricts the passive diffusion of molecules from the bloodstream into the brain. A deficiency of pericytes leads to a more permeable, or “leaky,” BBB, compromising the brain’s protected status.
This regulation of molecular traffic is distinct from their role in controlling blood flow. The BBB function is about selective permeability—controlling which molecules can pass from the blood into brain tissue. Pericytes also influence vesicle trafficking, another method by which substances are transported across the endothelial cell layer.
Role in Disease Progression
When pericyte function is compromised, the stability and regulation of the microvasculature can break down, contributing to a range of diseases. Dysfunctional pericytes are implicated in the progression of several disorders.
- In neurodegenerative conditions like Alzheimer’s disease, pericyte loss contributes to the breakdown of the blood-brain barrier, which can accelerate the accumulation of toxic proteins in the brain.
- Following a stroke, the constriction and death of pericytes can cause a sustained reduction in blood flow and increased BBB permeability, worsening neuronal damage.
- In diabetic retinopathy, a leading cause of blindness, the loss of pericytes from retinal capillaries is one of the earliest pathological changes, leading to microaneurysms and vascular leakage.
- In cancer, pericytes are recruited to stabilize the new blood vessels that tumors create to supply themselves with nutrients, thereby supporting tumor growth.