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.
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.
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.
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.
Research has shown that people with Alzheimer's disease or vascular dementia tend to have leakier blood-brain barriers compared to healthy older adults. The blood-brain barrier is crucial for protecting the brain and also helps clear out harmful substances, like Aβ protein. In healthy brains, pericytes—support cells that wrap around capillaries—play a major role in maintaining the blood-brain barrier and clearing Aβ. This showed that there is a zonation in their expression patterns by which they can be grouped into different subsets, but no singular markers have been found so far that can identify unequivocally any of the cell types.