Arterial vs venous expression of genes: differences in inflammatory genes

Arteries and veins modulate cardiovascular homeostasis and contribute to the pathogenesis of hypertension. Functional differences between normal arteries and veins are based upon differences in gene expression. To better characterize these expression patterns, and to identify candidate genes that could be manipulated selectively in the venous system, we performed whole genome expression profiling of rat arteries and veins using the CodeLink platform. We used the major artery and vein of the rat, the thoracic aorta and caudal vena cava, respectively. Expression of mRNA for thrombospondins (TSP-1, 2, 4) was greater than 5-fold higher in veins vs arteries. The most prominent gene expression difference between the normal aorta and vena cava was pancreatitis associated protein (PAP1), a protein with anti-inflammatory functions that was 64-fold higher in vena cava vs aorta. Higher mRNA expression of TSP-1, TSP-2, TSP-4 and PAP1 in vena cava vs aorta was confirmed with real time RT-PCR. Importantly, immunohistochemical analysis of blood vessels sections qualitatively confirmed a higher expression of proteins in vena cava vs aorta. These studies report a difference in inflammatory genes in arteries vs veins. A particularly notable finding is the discovery of PAP1 mRNA and protein expression in peripheral blood vessels with a substantially higher expression in the veins. Data from these studies may provide novel insights into the genetic basis for functional differences between arteries and veins in health and disease.动脉与静脉可调节心血管稳态，并参与高血压的发病机制。正常动脉与静脉的功能差异源于基因表达的差异。为了更好地阐明此类表达模式，并筛选可在静脉系统中选择性调控的候选基因，本研究采用CodeLink平台对大鼠动脉与静脉进行全基因组表达谱分析。本次研究选取大鼠的主要动脉与静脉——胸主动脉（thoracic aorta）和下腔静脉（caudal vena cava）分别作为研究对象。血小板反应蛋白（thrombospondins, TSP-1、2、4）的mRNA表达量在静脉中较动脉高5倍以上。正常胸主动脉与下腔静脉之间最显著的基因表达差异为胰腺炎相关蛋白（pancreatitis associated protein, PAP1）——这种具有抗炎功能的蛋白在下腔静脉中的表达量较胸主动脉高64倍。实时定量逆转录聚合酶链反应（real time RT-PCR）验证了下腔静脉中TSP-1、TSP-2、TSP-4及PAP1的mRNA表达量更高。值得注意的是，对血管切片进行的免疫组织化学分析也从定性层面证实，下腔静脉中的蛋白表达量高于胸主动脉。本研究揭示了动脉与静脉间炎症相关基因的表达差异。尤为值得关注的发现是，外周血管中存在PAP1的mRNA与蛋白表达，且该蛋白在静脉中的表达量显著更高。本研究数据可为阐明健康与疾病状态下动脉与静脉功能差异的遗传基础提供全新视角。