TY - JOUR
T1 - Insights from systems pharmacology into cardiovascular drug discovery and therapy
AU - Li, Peng
AU - Fu, Yingxue
AU - Ru, Jinlong
AU - Huang, Chao
AU - Du, Jiangfeng
AU - Zheng, Chunli
AU - Chen, Xuetong
AU - Li, Pidong
AU - LYU, Aiping
AU - Yang, Ling
AU - Wang, Yonghua
N1 - This work is supported by grants from Northwest A & F University, National Natural Science foundation of China (11201049 and 31170796). It was partially supported by China Academy of Chinese Medical Sciences (ZZ0608), and National ‘973’ Program of China (2013CB531805).
Publisher Copyright:
© 2014 Li et al.
PY - 2014/12/24
Y1 - 2014/12/24
N2 - Background: 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. Results: 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. Conclusions: All these provide important consensus as to the cause, prevention, and treatment of various CVD disorders from systems-level perspective.
AB - Background: 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. Results: 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. Conclusions: All these provide important consensus as to the cause, prevention, and treatment of various CVD disorders from systems-level perspective.
KW - Cardiovascular disease
KW - Drug discovery
KW - Drug-target network
KW - Gene-disease network
KW - Network analysis
KW - Network pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85027927068&partnerID=8YFLogxK
U2 - 10.1186/s12918-014-0141-z
DO - 10.1186/s12918-014-0141-z
M3 - Journal article
C2 - 25539592
AN - SCOPUS:85027927068
SN - 1752-0509
VL - 8
JO - BMC Systems Biology
JF - BMC Systems Biology
IS - 1
M1 - A2210
ER -