Abdominal aortic aneurysm(AAA)is a permanent dilatation of the abdominal aorta and is highly lethal.The main purpose of the current study is to search for noninvasive medical therapies for AAA,for which there is curre...Abdominal aortic aneurysm(AAA)is a permanent dilatation of the abdominal aorta and is highly lethal.The main purpose of the current study is to search for noninvasive medical therapies for AAA,for which there is currently no effective drug therapy.Network medicine represents a cuttingedge technology,as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective.Here,we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases.Analysis revealed some patterns for these diseases.For instance,diseases tended to be clustered and coherent in the network.Surprisingly,we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus,both of which are autoimmune diseases,suggesting that AAA could be one type of autoimmune diseases in etiology.Based on this observation,we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA.Finally,animal experiments confirmed that methotrexate,a drug for autoimmune diseases,was able to alleviate the formation and development of AAA.展开更多
基金supported by the grants from the PKUBaidu Fund(Grant No.2019BD014)the National Natural Science Foundation of China(Grant Nos.81970440 and 62025102 to Qinghua CuiGrant Nos.31930056,81730010,and 91539203 to Wei Kong).
文摘Abdominal aortic aneurysm(AAA)is a permanent dilatation of the abdominal aorta and is highly lethal.The main purpose of the current study is to search for noninvasive medical therapies for AAA,for which there is currently no effective drug therapy.Network medicine represents a cuttingedge technology,as analysis and modeling of disease networks can provide critical clues regarding the etiology of specific diseases and therapeutics that may be effective.Here,we proposed a novel algorithm to quantify disease relations based on a large accumulated microRNA–disease association dataset and then built a disease network covering 15 disease classes and 304 diseases.Analysis revealed some patterns for these diseases.For instance,diseases tended to be clustered and coherent in the network.Surprisingly,we found that AAA showed the strongest similarity with rheumatoid arthritis and systemic lupus erythematosus,both of which are autoimmune diseases,suggesting that AAA could be one type of autoimmune diseases in etiology.Based on this observation,we further hypothesized that drugs for autoimmune diseases could be repurposed for the prevention and therapy of AAA.Finally,animal experiments confirmed that methotrexate,a drug for autoimmune diseases,was able to alleviate the formation and development of AAA.
