Functional analysis of meltrin β/ADAM 19 in formation of the cardiac coronary artery

ADAMs（一种崩解素和金属蛋白酶）家族被认为是膜锚定糖蛋白，包含金属蛋白酶和崩解素结构域，并参与各种膜锚定蛋白、生长因子、细胞间信号分子和粘附分子的外胞域脱落。ADAMs在多种生物过程中发挥重要作用，包括神经发生、受精、血管生成、心脏发生和癌症。Meltrin β/ADAM19是ADAMs缺陷小鼠的成员，表现为室间隔缺损和不成熟的瓣膜形成。心肌神经嵴细胞中表达的Meltrin β是室间隔和瓣膜形成所必需的。缺Meltrin β的神经嵴细胞可正常迁移至心脏，但不能正常融合近端流出道缓冲组织的两嵴。这就导致了室间隔膜的缺损。Meltrin β缺乏小鼠冠状动脉出现动脉瘤、上斜、口状异常，形成冠状动静脉瘘，流入室间隔，直接与心室相连。在室间隔冠状动脉的室间隔分支似乎形成了一个巨大的肿块，形成了另一个新的心室。我们可以发现冠状动脉中隔血流在收缩期表现为反流。

ADAMs (a disintegrin and metalloprotease) family are known to be membrane-anchored glycoproteins that contain metalloprotease and disintegrin domains, and participate in the ectodomain shedding of various membrane-anchored proteins, growth factors, intercellular signaling molecules, and adhesion molecules. ADAMs play important roles in a variety of biological processes, including neurogenesis, fertilization, angiogenesis, cardiogenesis and cancer. Meltrin β/ADAM19 which is a member of the ADAMs deficient mice showed ventricular septal defect and immature valve formation. Meltrin β expressed in cardiac neural crest cells is required for ventricular septum and valve formations. Meltrin β-deficient neural crest cells migrated into the heart normally, however, they could not properly fuse the both ridges of the cushion tissues in the proximal outflow tract. Then this let to defect the membranous of the ventricular septum. Meltrin β-deficient mice showed anomalies of the coronary arteries which are aneurysm, surpentine, and orifice, formed coronary arteriovenous fistula that is influent into the ventricular septum and connected to the ventricle directly. In the ventricular septum the septum branch of the coronary artery seems like to form a big mass as a new another ventricle. We could find the blood flow of the septum coronary artery showed the regurgitant flow during systolic.