The role of endothelial tryptophan hydroxylase in pulmonary vascular remodelling: an integrated approach

5-羟色胺是一种化学物质，可以作用于肺血管，使其变厚。这会导致肺部的高血压。负责合成影响肺部的5-羟色胺的酶是色氨酸羟解酶1。血管有三层，外层是外膜细胞，另一层是肌肉层，内层是称为内皮细胞的细胞。我们将确定色氨酸羟解酶1是否导致内皮细胞合成5-羟色胺，然后这种5-羟色胺是否能作用于邻近的肌肉和外膜细胞，使它们生长并导致动脉增厚。我们还将确定缺氧(氧气的减少)是否可以刺激内皮细胞5-羟色胺合成和释放的增加，以及这是否有助于缺氧诱导的血管增厚。在我们的研究中，我们将使用缺乏色氨酸羟水解酶1的转基因小鼠，以及分离的平滑肌、外膜和内皮细胞。我们还将使用新的基因转移技术检查在整个动物的内皮细胞中敲除色氨酸羟解酶1的羽毛能力。

Serotonin is a chemical that can act on the blood vessels of the lungs to cause them to thicken. This can lead to high blood pressure in the lungs. The enzyme responsible for the synthesis of serotonin that affects the lungs is tryptophan hydroxlase 1. Blood vessels have three layers, an outer layer of adventitial cells, a muscular layer and an inner layer of cells called endothelial cells. We will determine if tryptophan hydroxlase 1 causes synthesis of serotonin by the endothelial cells and if this serotonin can then act on the adjacent muscle and adventitial cells to make them grow and cause thickening of the artery. We will also determine if hypoxia (a reduction in oxygen) can stimulate an increase in endothelial cell serotonin synthesis and release and that this contributes to hypoxia-induced thickening of the blood vessels. We will use genetically modified mice which lack tryptophan hydroxlase 1 in our studies as well as isolated smooth muscle, adventitial and endothelial cells. We will also examine the feasilbility of knocking out tryptophan hydroxlase 1 in the endothelial cells in the whole animal using novel gene transfer techniques.