Heart, Aorta and Aortic Valve Development and Cardiovascular Malformations

Abstract

IntroductionIn vertebrates, the heart is the first organ to develop and takes shape during the third week of embryogenesis. The earliest evidence of a heart structure can be identified beginning from day 15 of pregnancy. Stem cells in the anterior-lateral mesoderm become specific cardiac precursor cells and align in a horseshoe shape. In the third week of pregnancy these heart precursor cells that are previously arranged in bilateral symmetrical manner move medially to unite and form a single primitive heart tube. This straight heart tube consists of an inner cell layer (endocardium), an outer cell layer (myocardium), and the extracellular matrix (ECM) separating the other two layers also known as the heart jelly.The developmental stage that follows is a right-hand rotation of the heart leading to the first left-right non-symmetry in the embryo. Because of this rotation, the segments of the heart tube that later form the atria are positioned above the segment that forms the ventricles. The atria, ventricles, and truncus arteriosus originate through local extensions of the heart tube during heart loop shaping. Simultaneously, the ECM within the outflow tract and the future atrioventricular channel expand to form so-called endocardial cushions. Heart-tube segmentation into atria, ventricles, and the outflow tract is accomplished by these cushions. By further growth and additional fusions, they form septum-and valve-structure precursors, separating the developing ventricles from each other.During the sixth and seventh week of pregnancy, the heart and the common outflow tract (truncus arteriosus) are chambered by the septa to divide into four distinct ventricles, the aorta, and the pulmonary artery. This results in the formation of a separate pulmonary and systemic circulation. The aorta and its respective segments originate from diverse embryonic structures. The ascending part of the aorta, the aorta ascenders is formed by the division of the truncus arteriosus as described above; however, the aortic arch and supra-aortic vessels originate from the third and fourth branchial arch arteries. The fivecomplete branchial arch artery pairs are also designated as aortic arches and originate from the truncus arteriosus, connecting it with the right and left dorsal aorta, which are also a part of the embryonic circulation. When the heart develops into the heart tube, valve morphogenesis also begins. The ECM in regions around the outflow tracts and between the atria and ventricles expand to form endocardial cushions, contributing to the formation of all four heart valves. During the next few days interactions between diverse endocardial and myocardial signals occur, which are of crucial importance for the transition remodeling of the endothelium and the mesenchyme. Following this transformation, mesenchymal cells proliferate and support further swelling of the endocardial cushions. In addition, myocardial cells infiltrate the edges of the endocardial cushions now containing mesenchymal cells [1][2][3][4][5].In the truncus ar...