Li Peng, Fu Yingxue, Ru Jinlong, Huang Chao, Du Jiangfeng, Zheng Chunli, Chen Xuetong, Li Pidong, Lu Aiping, Yang Ling, Wang Yonghua
Center of Bioinformatics, College of Life Science, Northwest A and F University, Yang ling, Shaanxi, 712100, China.
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
BMC Syst Biol. 2014 Dec 24;8:141. doi: 10.1186/s12918-014-0141-z.
Given the complex nature of cardiovascular disease (CVD), information derived from a systems-level will allow us to fully interrogate features of CVD to better understand disease pathogenesis and to identify new drug targets.
Here, we describe a systematic assessment of the multi-layer interactions underlying cardiovascular drugs, targets, genes and disorders to reveal comprehensive insights into cardiovascular systems biology and pharmacology. We have identified 206 effect-mediating drug targets, which are modulated by 254 unique drugs, of which, 43% display activities across different protein families (sequence similarity < 30%), highlighting the fact that multitarget therapy is suitable for CVD. Although there is little overlap between cardiovascular protein targets and disease genes, the two groups have similar pleiotropy and intimate relationships in the human disease gene-gene and cellular networks, supporting their similar characteristics in disease development and response to therapy. We also characterize the relationships between different cardiovascular disorders, which reveal that they share more etiological commonalities with each other rooted in the global disease-disease networks. Furthermore, the disease modular analysis demonstrates apparent molecular connection between 227 cardiovascular disease pairs.
All these provide important consensus as to the cause, prevention, and treatment of various CVD disorders from systems-level perspective.
鉴于心血管疾病（CVD）的复杂性，从系统层面获取的信息将使我们能够全面探究CVD的特征，以更好地理解疾病发病机制并确定新的药物靶点。
在此，我们描述了对心血管药物、靶点、基因和疾病之间多层相互作用的系统评估，以揭示对心血管系统生物学和药理学的全面见解。我们确定了206个效应介导药物靶点，这些靶点由254种独特药物调节，其中43%在不同蛋白质家族（序列相似性<30%）中表现出活性，突出了多靶点治疗适用于CVD这一事实。尽管心血管蛋白质靶点与疾病基因之间几乎没有重叠，但两组在人类疾病基因-基因和细胞网络中具有相似的多效性和密切关系，支持它们在疾病发展和对治疗反应方面的相似特征。我们还描述了不同心血管疾病之间的关系，这表明它们在全球疾病-疾病网络中彼此共享更多病因共性。此外，疾病模块分析表明227对心血管疾病之间存在明显的分子联系。
所有这些从系统层面的角度为各种CVD疾病的病因、预防和治疗提供了重要的共识。
