Mural cells are a generalized cell population in the microcirculation that comprises vascular smooth muscle cells (vSMCs), and pericytes. Both types are in close contact with the endothelial cells lining the capillaries, and are important for vascular development and stability. The vasculature is a system of small, interconnected tubes that ensure there is proper blood flow to all of the organs. Mural cells are involved in the formation of normal vasculature and are responsive to factors including platelet-derived growth factor B (PDGFB) and vascular endothelial growth factor (VEGF). The weakness and disorganization of tumor vasculature is partly due to the inability of tumors to recruit properly organized mural cells.
Function during angiogenesis Mural cells, like pericytes, are important for how blood vessels work. During the growth of new blood vessels (a process called angiogenesis), pericytes help guide how endothelial cells grow and divide. This process relies on the ability of pericytes to contract. In developing mouse retinas, endothelial cells produce a signal called Pdgfb that attracts pericytes to the area where new blood vessels are forming. Pericytes also help control the amount of a growth factor called Vegfa by using a receptor (Vegfr1) that soaks it up. Without pericytes, there's too much Vegfa, which messes up how the blood vessels grow and branch.
Other research shows that pericytes release a protein called angiopoietin 1, which also helps control new blood vessel growth. Adding extra angiopoietin 1 can fix the blood vessel problems caused by a lack of pericytes. This signaling also helps keep pericytes alive and in place. In fact, removing the receptor for angiopoietin (Tie2) in pericytes can lead to more blood vessel growth in tumors, making them grow faster.
Overall, healthy blood vessel growth depends on teamwork between endothelial cells and pericytes. After the blood vessels have formed, pericytes also help fine-tune the network by causing some vessels to shrink and disappear.
Establishment and regulation of the blood-brain barrier Besides helping with blood vessel growth, mural cells like pericytes also play key roles in shaping blood vessels in specific organs. One important job they have is helping to build and maintain the blood–brain barrier—a protective shield that keeps harmful substances out of the brain.
The blood-brain barrier is made up of endothelial cells, pericytes, and the ends of astrocyte cells, all sitting on a shared support structure called the basement membrane. Pericytes help control how much passes through the blood-brain barrier by managing how endothelial cells move substances across their surface, how astrocyte ends are positioned, and by stopping unwanted proteins from building up in the brain. They also help endothelial cells form tight seals, known as tight junctions, between cells, which are crucial for keeping the barrier strong.
Pericytes can even influence which genes are turned on or off in endothelial cells. Overall, these mural cells work closely with endothelial cells to form and maintain the specialized blood vessels that different organs need—especially in the brain.
Regulation of blood vessel diameters and flow Once blood vessels are fully developed, mural cells help manage how blood moves through the brain—a process called neurovascular coupling. This ensures that active areas of the brain get more blood when needed, a response known as functional hyperaemia. Smooth muscle cells (SMCs) are well known for their ability to contract and relax, which allows them to adjust blood vessel width and regulate flow. How strongly these cells contract directly affects how much blood can pass through.
There is still ongoing debate about how much pericytes contribute to this process. Some researchers suggest dividing pericytes into subtypes—like ensheathing, mesh, and thin-strand pericytes—but the scientific community hasn’t reached agreement on these classifications yet, and terms like "capillary pericytes" are still used inconsistently.
When the brain is active, neurons and nearby support cells (astrocytes) release chemical signals that tell mural cells to either tighten or loosen, which changes the size of the blood vessels and directs blood to where it’s needed. A key molecule involved in this process is nitric oxide, which helps widen arterioles. On the other hand, astrocytes use a different molecule, arachidonic acid, to help open up smaller capillaries. These findings show that SMCs and pericytes may have distinct roles depending on the type and size of blood vessel involved.
In skeletal muscles, blood vessel widening and narrowing is carefully coordinated across branches to ensure muscles get enough oxygen during activity. This coordination is mostly handled by the sympathetic nervous system, which balances increased local blood flow with overall blood pressure. Nitric oxide from muscle cells or endothelial cells plays a role here too. In addition, sympathetic nerves release several chemicals—including noradrenaline and neuropeptide Y—that cause SMCs to contract, narrowing the vessels. Interestingly, the specific signals and receptors that control blood flow vary between the brain and other parts of the body. This highlights how mural cells adapt to the unique needs of different organs. Understanding how all these systems work together throughout the body remains a key area for future study.
Cell type controversy
Mural cells were described for the first time in the late 19th century as contractile cells lining up around the endothelium. In reality, it was a variety of cells that had been observed and bundled up under the common name of Rouget cells. Later studies brought controversy about their contractility, and this remains an elusive point today.
Pericytes, vSMCs, and many other perivascular cell types express very similar markers such as Platelet Derived Growth Factor Receptor Beta (PDGFR-B), aminopeptidase-N (CD13), chondroitin sulfate proteoglycan 4 (Ng2), or desmin, which makes their identification difficult and requires a combination of markers: for example vSMCs but not pericytes express alpha-smooth muscle actin (ACTA2). Nowadays, distinctively characterizing these cells requires a combination of markers, cellular location and morphology.
Role in cardiovascular disease and treatment At one extreme, losing mural cells can weaken the support structure around blood vessels, particularly the endothelial barrier, which may lead to vascular problems. Scientist Juchem and colleagues found that mural cells may actually encourage blood clot formation, which can contribute to a condition called coronary no-reflow. This condition occurs when blood fails to return properly to the heart's small vessels after a blockage is cleared.
Mural cells are a major source of tissue factor (TF), a protein that helps start the body’s clotting process. When inflammation affects the heart's small vessels, it can trigger mural cells to release TF, kicking off a chain reaction that leads to blood clots and blocked vessel pathways. Also, mural cells may contribute to blocked blood flow by physically tightening and narrowing these vessels. In heart attack patients, this has been linked to higher levels of endothelin-1, a molecule that promotes vessel constriction. This results in an increase in contractile mural cells (marked by αSMA expression) and narrower vessel openings. These effects have also been seen in lab models of ischemia-reperfusion injury, pointing to mural cells as key players in no-reflow complications.
While vascular smooth muscle cells (VSMCs) are usually tied to atherosclerosis, mural cells have also been found in the inner layers of arteries. In mouse studies, after blood vessel injury, mural cells marked by NG2, PDGFRβ, and CD146 increased in the outer layer of blood vessels (adventitia) and moved inward. Since mural cell dysfunction is closely linked to fibrosis in the kidneys, researchers think a similar process might happen in the heart.
In heart disease, inflammatory immune cells like macrophages can release a protein called galectin-3, which causes mural cells to multiply and produce procollagen 1—a precursor to the collagen that forms scar tissue. This may lead to cardiac fibrosis. Additionally, heart mural cells may transform into myofibroblasts—the main cells responsible for producing scar tissue—when triggered by inflammation or TGFβ signaling. Some studies suggest this transformation happens in heart conditions like fibrocalcific aortic valve disease, where new blood vessel growth in the valve is strongly linked to disease progression. Notably, mural cells are frequently found near these new vessels and may contribute to the buildup of fibrous and calcified tissue.
Even though researchers are still figuring out how mural cells affect more common heart issues—like heart failure with preserved ejection fraction (HFpEF), heart enlargement (hypertrophy), or structural changes after damage—the topic is seen as highly promising and deserves more attention.
Encouragingly, recent research by Chen et al. showed the therapeutic potential of mural cells in heart repair. When mural cells taken from human skeletal muscle were injected into mice with heart damage, they significantly improved heart function. These cells helped rebuild heart tissue, reduced scarring, improved heart structure, and encouraged the growth of new blood vessels. The reduction in fibrosis was likely due to matrix metalloproteinases (MMPs) released by the mural cells. They also reduced inflammation by lowering the number of immune cells entering the damaged heart. Beyond heart disease, mural cells are already being explored as a promising cell therapy tool in other medical conditions, but research is still being conducted.
Synchronous calcium activity and vasomotion In many organs, small blood vessels such as arterioles, capillaries, and venules exhibit rhythmic contractions known as vasomotion. These spontaneous contractions are thought to help regulate blood flow into tissues and support waste removal. They are not primarily driven by nervous or hormonal signals but arise from the inherent electrical and chemical activity of mural cells—which include vascular smooth muscle cells (VSMCs) and pericytes.
A key driver of vasomotion is the synchronous release of calcium (Ca²⁺) within mural cells. These calcium signals, or spontaneous Ca²⁺ transients, originate from internal stores (the sarcoendoplasmic reticulum or SR/ER) and are coordinated through electrical connections between cells via gap junctions. This allows the signal to spread through a network of mural cells, ensuring coordinated contractions.
The calcium release is regulated by IP3 and ryanodine receptors in the SR/ER. Once released, Ca²⁺ activates calcium-activated chloride channels (CaCCs), causing membrane depolarization. This depolarization, in turn, opens voltage-dependent calcium channels (VDCCs)—both T-type and L-type—further amplifying calcium influx and synchronizing activity across cells.
The ability of mural cells to stay in sync also depends on maintaining the resting membrane potential within a narrow range. This is controlled by potassium channels such as Kv7 and inward rectifier K⁺ channels (Kir). If the membrane is too depolarized, the cells may fire irregularly; if too hyperpolarized, they may not fire at all. Disruption of this balance leads to loss of synchronized calcium transients and impaired vasomotion.