Abstract
Salvia miltiorrhiza, known as Danshen, has attracted worldwide interest for its substantial effects on coronary heart disease (CHD). Danshensu (DSS) is one of the main active ingredients of Danshen on CHD. Although it has been proven to have a good clinical effect on CHD, the action mechanisms remain elusive. In the current study, a coexpression network-based approach was used to illustrate the beneficial properties of DSS in the context of CHD. By integrating the gene expression profile data and protein-protein interactions (PPIs) data, two coexpression protein interaction networks (CePIN) in a CHD state (CHD CePIN) and a non-CHD state (non-CHD CePIN) were generated. Then, shared nodes and unique nodes in CHD CePIN were attained by conducting a comparison between CHD CePIN and non-CHD CePIN. By calculating the topological parameters of each shared node and unique node in the networks, and comparing the differentially expressed genes, target proteins involved in disease regulation were attained. Then, Gene Ontology (GO) enrichment was utilized to identify biological processes associated to target proteins. Consequently, it turned out that the treatment of CHD with DSS may be partly attributed to the regulation of immunization and blood circulation. Also, it indicated that sodium/hydrogen exchanger 3 (SLC9A3), Prostaglandin G/H synthase 2 (PTGS2), Oxidized low-density lipoprotein receptor 1 (OLR1), and fibrinogen gamma chain (FGG) may be potential therapeutic targets for CHD. In summary, this study provided a novel coexpression protein interaction network approach to provide an explanation of the mechanisms of DSS on CHD and identify key proteins which maybe the potential therapeutic targets for CHD.
Highlights
Coronary heart disease (CHD) is a leading cause of morbidity and mortality globally
The mechanisms of DSS were illuminated by a coexpression protein interaction network (CePIN), which would probably be beneficial for the development of targets for coronary heart disease (CHD) therapeutic intervention
The results identified the unique-bottlenecks fibrinogen gamma chain (FGG) and SLC9A3 as the targets of DSS in the treatment of CHD, which were potential targets for new drug design
Summary
Coronary heart disease (CHD) is a leading cause of morbidity and mortality globally. It is a common disease associated with vascular stenosis or obstruction caused by coronary artery vascular lesions [1]. An established traditional Chinese medicine (TCM) with 1000 years of clinical application, can promote blood circulation and eliminate blood stasis [2,3]. It has been extensively used in the treatment of CHD. The mechanisms of DSS were illuminated by a coexpression protein interaction network (CePIN), which would probably be beneficial for the development of targets for CHD therapeutic intervention. The protein interaction network (PIN) oIfnDtShSewmaiscrsohoawrrnayindFaigtau,rtehSe1.coexpression is reflected by strong correlations between expression levels, wIhniltehenomtiacrlol acrhraanygdeastai,nthceoecxopexrpersessiosinonarisermefalencitfeedstbeydsbtryonugpc-oorrredlaotwionns-rbeegtwuleaetnioenxporfeisnsidoinvidual genelsev[1el1s,,1w6–h1il8e]n. FFiigguurree22..(A(A) )CCoeoxepxrpersessiosinopnroptreointeiinnteirnatcetriaocntinoentwnoertwkso(rCkesP(ICNe)PinINa)nionn-aCHnoDn-sCtaHteD(nsotna-tCe H(nDonC-eCPHIND) aCnedPI(NB)) caonedxp(Bre)scsiooenxpprreostseiionninptreortaecintioinntneeratwctoiornksn(eCtwePoIrNks) i(nCaePCINH)DinstaateC(HCDHDstaCteeP(ICNH).DNCoedPeIsNin). gNroeednescionlogrreaeren uconlioqruaerneoudneisquine nnoond-eCs HinDnCone-PCINH;DthCoesPeINin; ytheollsoewincoyleolrloawrecsohloarreadrensohdaersedbontohdiens nboonth-CinHnDonC-eCPHIND CanedPICNHaDndCCeHPIDNC; tehPoIsNe; itnhopsienikncpoilnokr caorleour nariqeuueninqoudeensoidneCs HinDCHCeDPCINeP; IaNnd, atnhde; bthlaecbkllaincekslianrees ianrteerianctetiroancstiobnetswbeeetnwneeondenso. des
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