Dyer Laura A, Rugonyi Sandra
Department of Biology, University of Portland, Portland, OR 97203, USA.
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA.
J Cardiovasc Dev Dis. 2021 Jul 30;8(8):90. doi: 10.3390/jcdd8080090.
In congenital heart disease, the presence of structural defects affects blood flow in the heart and circulation. However, because the fetal circulation bypasses the lungs, fetuses with cyanotic heart defects can survive in utero but need prompt intervention to survive after birth. Tetralogy of Fallot and persistent truncus arteriosus are two of the most significant conotruncal heart defects. In both defects, blood access to the lungs is restricted or non-existent, and babies with these critical conditions need intervention right after birth. While there are known genetic mutations that lead to these critical heart defects, early perturbations in blood flow can independently lead to critical heart defects. In this paper, we start by comparing the fetal circulation with the neonatal and adult circulation, and reviewing how altered fetal blood flow can be used as a diagnostic tool to plan interventions. We then look at known factors that lead to tetralogy of Fallot and persistent truncus arteriosus: namely early perturbations in blood flow and mutations within VEGF-related pathways. The interplay between physical and genetic factors means that any one alteration can cause significant disruptions during development and underscore our need to better understand the effects of both blood flow and flow-responsive genes.
在先天性心脏病中，结构缺陷的存在会影响心脏内的血流和循环。然而，由于胎儿循环绕过肺部，患有青紫型心脏缺陷的胎儿在子宫内能够存活，但出生后需要及时干预才能存活。法洛四联症和永存动脉干是最严重的圆锥动脉干心脏缺陷中的两种。在这两种缺陷中，血液进入肺部受到限制或无法进入，患有这些严重病症的婴儿在出生后需要立即进行干预。虽然已知有导致这些严重心脏缺陷的基因突变，但早期的血流扰动也可独立导致严重心脏缺陷。在本文中，我们首先比较胎儿循环与新生儿及成人循环，并回顾如何将改变的胎儿血流用作诊断工具来规划干预措施。然后，我们研究导致法洛四联症和永存动脉干的已知因素：即早期的血流扰动和血管内皮生长因子（VEGF）相关途径内的突变。物理因素与遗传因素之间的相互作用意味着任何一种改变都可能在发育过程中造成重大破坏，并突出了我们更好地了解血流和血流反应基因影响的必要性。
