Ran Jihua, Li Hui, Fu Jianfeng, Liu Ling, Xing Yanchao, Li Xiumei, Shen Hongming, Chen Yan, Jiang Xiaofang, Li Yan, Li Huiwu
Basic Medicine School, Xinjiang Medical University, Urumqi, Xinjiang, China.
BMC Syst Biol. 2013 Apr 12;7:32. doi: 10.1186/1752-0509-7-32.
Essential hypertension (EH) is a complex disease as a consequence of interaction between environmental factors and genetic background, but the pathogenesis of EH remains elusive. The emerging tools of network medicine offer a platform to explore a complex disease at system level. In this study, we aimed to identify the key proteins and the biological regulatory pathways involving in EH and further to explore the molecular connectivities between these pathways by the topological analysis of the Protein-protein interaction (PPI) network.
The extended network including one giant network consisted of 535 nodes connected via 2572 edges and two separated small networks. 27 proteins with high BC and 28 proteins with large degree have been identified. NOS3 with highest BC and Closeness centrality located in the centre of the network. The backbone network derived from high BC proteins presents a clear and visual overview which shows all important regulatory pathways for blood pressure (BP) and the crosstalk between them. Finally, the robustness of NOS3 as central protein and accuracy of backbone were validated by 287 test networks.
Our finding suggests that blood pressure variation is orchestrated by an integrated PPI network centered on NOS3.
原发性高血压(EH)是一种由环境因素与遗传背景相互作用导致的复杂疾病,但其发病机制仍不清楚。新兴的网络医学工具为在系统层面探索复杂疾病提供了一个平台。在本研究中,我们旨在识别参与EH的关键蛋白质和生物调节途径,并通过蛋白质-蛋白质相互作用(PPI)网络的拓扑分析进一步探索这些途径之间的分子连接性。
扩展网络包括一个由535个节点通过2572条边连接而成的巨型网络和两个分离的小网络。已鉴定出27个具有高介数中心性(BC)的蛋白质和28个具有大度的蛋白质。BC和接近中心性最高的一氧化氮合酶3(NOS3)位于网络中心。由高BC蛋白质衍生的骨干网络呈现出清晰直观的概述,显示了所有重要的血压调节途径以及它们之间的相互作用。最后,通过287个测试网络验证了NOS3作为中心蛋白质的稳健性和骨干网络的准确性。
我们的研究结果表明,血压变化是由以NOS3为中心的综合PPI网络协调的。