In the developing fetal heart, temporary structures known as endocardial cushions form in the atrioventricular canal, the central channel connecting the primitive upper and lower chambers. The development and fusion of these cushions are foundational to creating a healthy, four-chambered heart. Their growth separates the atria from the ventricles and forms the valves that regulate blood flow between them.
Formation and Composition
Endocardial cushions begin as expansions of the cardiac jelly, an extracellular matrix rich in proteins and hyaluronic acid that separates the heart’s inner lining (endocardium) from its outer muscular layer (myocardium). These regions of cardiac jelly swell in the atrioventricular canal and the outflow tract, the tube carrying blood out of the heart. The formation of the cushions is driven by a cellular process called epithelial-to-mesenchymal transition (EndMT).
During EndMT, signals from the myocardium induce stationary endothelial cells to transform into mobile mesenchymal cells. This transformation allows them to detach from the endocardial layer and invade the cardiac jelly, populating it and causing it to swell into the cushion structures. This process is tightly regulated by a network of signaling pathways, ensuring the cushions form at the correct time and place.
The population of the cardiac jelly with these mesenchymal cells creates the cushion primordia. These structures are not static and continue to grow and remodel as development proceeds. This initial formation is a prerequisite for dividing the heart’s chambers and forming its valve systems, as subsequent steps of heart maturation depend on it.
Role in Heart Septation
The primary function of the endocardial cushions is the division, or septation, of the early heart tube into four chambers. In the atrioventricular canal, four cushions form: a superior, an inferior, and two smaller lateral cushions. The superior and inferior cushions, located on the top and bottom surfaces of the canal, are the main participants in septation. They grow progressively toward one another, extending into the heart’s central lumen.
This growth culminates in the fusion of the superior and inferior cushions around the sixth week of gestation. This fusion creates a barrier that divides the common atrioventricular canal into separate right and left orifices. This partitioning is a major step in separating the pathways for oxygen-poor blood on the right side of the heart and oxygen-rich blood on the left.
Beyond dividing the canal, the fused cushion mass serves as an anchor point for other developing septa. The septum primum, the initial wall from the roof of the primitive atrium, fuses with the cushion mass to close the gap between the atria. The fused cushions also contribute to the membranous portion of the interventricular septum, the wall separating the ventricles.
Development into Heart Valves
Once the cushions have fused, the tissue undergoes a second, equally important transformation. The mesenchymal cells and surrounding matrix are remodeled to form the leaflets of the atrioventricular valves. This process involves cell proliferation, programmed cell death (apoptosis), and matrix reorganization. The bulky cushions are gradually sculpted into thin, flexible, and highly durable valve leaflets.
The different cushions give rise to specific parts of the atrioventricular valves. The fused superior and inferior cushions develop into the anterior leaflet of the mitral valve (left side) and the septal leaflet of the tricuspid valve (right side). The left lateral cushion becomes the posterior leaflet of the mitral valve, while the right lateral cushion forms the anterior and posterior leaflets of the tricuspid valve.
This remodeling continues throughout fetal life and into the neonatal period. The mechanical forces of blood flow are thought to help shape the final structure of the valve leaflets. This transformation from a simple swelling into a functional valve ensures that blood flows in only one direction, from the atria to the ventricles.
Endocardial Cushion Defects
When endocardial cushions fail to fuse correctly, it results in a congenital heart condition called an atrioventricular septal defect (AVSD). This condition, previously known as an endocardial cushion defect, leaves a hole in the center of the heart that disrupts the separation of its chambers. The consequences of an AVSD depend on its severity and anatomy.
AVSDs are generally classified into two main types: partial and complete. A partial AVSD typically involves a hole in the atrial septum (an ostium primum defect) and an abnormally formed mitral valve, often with a cleft in it. In a complete AVSD, the failure of fusion is more extensive, resulting in a large central hole allowing communication between all four heart chambers. Individuals with a complete AVSD have a single, common atrioventricular valve instead of two separate ones.
The physiological result of an AVSD is the mixing of oxygenated blood from the left side of the heart with deoxygenated blood from the right side. This leads to increased blood flow to the lungs, which can elevate pressure in the pulmonary arteries and force the heart to work harder, potentially leading to heart failure. There is a strong association between AVSDs and genetic conditions, most notably Down syndrome (Trisomy 21), for which it is a common cardiac finding.