Development of the cardiovascular system
Organ system development
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Development of the cardiovascular system
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Content Reviewers:Rishi Desai, MD, MPH, Yifan Xiao, MD
Contributors:Tanner Marshall, MS, Evan Debevec-McKenney
The cardiovascular system starts developing at the beginning of week 3 of intrauterine life.
At that point, the embryo is a flat little pancake made up of two layers: the epiblast on the dorsal, or back, side, and the hypoblast on the ventral, or front, side.
A line called the primitive streak appears on the epiblast back of this two-layered creature.
Cells migrate along the primitive streak during gastrulation, resulting in a three-layered embryo pancake, with each layer containing germ cells that form organs and tissues of the body.
The ventral, or bottom, germ layer is called endoderm, the dorsal, or top, germ layer is called ectoderm, and the layer in between these two is called mesoderm.
The heart derives from a part of the mesoderm called the visceral mesoderm.
Let’s look at this three-week-old creature from above. Mesoderm cells go through the primitive streak and make their way up to the embryo’s head, forming an area that’s called the primary heart field, a horseshoe-shaped area that has two limbs, with one on either side of the future brain.
This region lies on a blanket of endoderm cells that secrete vascular endothelial growth factor, which is called VEGF for short.
VEGF signals the cells in the limbs of the horseshoe to self-organize into two heart tubes.
A primitive pericardial cavity also appears lateral to each endocardial tube.
At its inferior end, each endocardial tube connects to a vitelline vein, which comes from an extraembryonic tissue called the yolk sac and through which blood enters the endocardial tube.
Blood exits each endocardial tube at its superior end through a dorsal aorta, which then continues down the embryo’s back.
During lateral folding, the flat embryo goes from a trilaminar disc to a more cylindrical shape.
The lateral borders of the embryo reach out towards each other and meet anteriorly at the midline, forming a cylindrical shape.
This process makes the two endocardial tubes fuse into one, forming the primitive heart tube.
The left and right vitelline veins also fuse to form the sinus venosus, which is the inflow tract of the heart tube.
Similarly, the aortae fuse to form the aortic sac, which is the outflow tract of the heart tube.
The two pericardial cavities also unite around the heart tube and form the singular pericardial cavity.
The heart tube remains attached to the back wall of the pericardial cavity by a sheet of mesoderm called the dorsal mesocardium.
The heart tube itself has two layers: an endothelial lining on the inside, which turns into the endocardium, and cardiac myoblasts on the outside, which become the myocardium.
Some of the myocardial cells in the sinus venosus begin to produce a rhythmic electrical discharge at this early stage.
However, the conduction system and working myocardium are still underdeveloped, and they can’t contract in perfect sync, so we don’t hear the familiar “lub-dub” of the heart at this point.
During craniocaudal folding, the now-cylindrical embryo curves down its length, forming more of a shrimp-like creature, and this process pushes the heart tube down towards the chest.
By the beginning of week 4, the heart tube reaches the thorax, and blood can be seen going through the heart tube.
The heart tube develops sections. First there’s the sinus venosus, which has a left and a right sinus horn that bring blood in.
Above it, there’s the primitive atrium and then the primitive ventricle, which are separated from one another by the atrioventricular sulcus.
The primitive atrium gives rise to the left and right atria, and the primitive ventricle forms the left ventricle.
The primitive ventricle is separated from the next region, called the bulbus cordis, by the bulboventricular sulcus.
The first part of the bulbus cordis forms the right ventricle, as well as the outflow tracts for both ventricles.
Finally, at the top of the heart tube, there’s the truncus arteriosus, which pumps blood through the aortic sac into an early version of the circulatory system that’s made up of aortic arches.
This organization of structures doesn’t mirror the adult heart, so during week 4 the heart tube undergoes looping, which is a fancy way of saying the tube elongates, its walls become thicker, and sections of the heart move around so that they end up in their right place.
The heart tube is held in place inside the pericardial cavity by blood vessels at both ends, and looping starts with the heart tube folding into a “C” shape.
The truncus arteriosus and bulbus cordis move down and to the right to form the top portion of the “C”, while the primitive ventricle bends to the right of the midline and a little to the front, forming the middle of the “C”.
Finally, the primitive atrium and sinus venosus form the bottom of the “C” and snuggle deeper inside the pericardial cavity.
As development continues, the growing ventricle moves to the left, so it crosses over the midline again, covering the primitive atrium.
By the end of week 4, the cardiac loop starts to take on the general appearance of the adult heart.
Also, by this point, visceral pericardium has attached to the outside of the heart, forming the epicardium.
The cardiovascular system develops at the beginning of week three during prenatal life. The development of the primitive heart starts with a horseshoe-shaped structure called the primary heart field, which has a pair of tubes that fold so that the heart structures will be in the proper position. Next, septa appear, which help to partition the heart into two atria and two ventricles.
The electrical conduction system of the primitive heart initially lies in the sinus venosus. As the sinus venous becomes absorbed by the right atria, the pacemaker cells appear in the sinoatrial node in the right atrium wall. The development of blood vessels involves the endothelium, which undergoes a process called angiogenesis, which is the formation of new blood vessels from pre-existing ones. This process is driven by growth factors such as VEGF (vascular endothelial growth factor).