Endotype-driven Co-module mechanisms of danhong injection in the Co-treatment of cardiovascular and cerebrovascular...

Area of Science:

• Integrative systems biology
• Pharmacogenomics
• Cardiovascular and cerebrovascular research

Background:

• Cardiovascular and cerebrovascular diseases are leading global causes of mortality.
• These conditions exhibit significant interdependencies.
• Danhong Injection (DHI) is a common treatment for co-existing brain and heart diseases (CTBH), but its molecular mechanisms are not fully understood.

Purpose of the Study:

• To elucidate the underlying molecular endotype mechanisms of Danhong Injection (DHI) in the co-treatment of brain and heart diseases (CTBH).

Main Methods:

• A modular-based disease and drug-integrated analysis (MDDIA) strategy was employed.
• High-throughput transcriptome-wide sequencing data from DHI treatment for stable angina pectoris (SAP) and cerebral infarction (CI) were analyzed.
• Module proximity-based topological analyses identified CTBH co-module pairs and driver genes, with in vitro validation of key genes.

Main Results:

• Seven DHI drug-targeted modules and three disease modules for SAP and CI were identified.
• Thirteen targeted module pairs and 17 driver genes related to DHI in CTBH were screened.
• In vitro experiments validated the role of driver genes AKT1, EDN1, and RHO.

Conclusions:

• This study integrated clinical sequencing data and modular analysis to understand DHI's CTBH mechanisms.
• The findings suggest DHI's efficacy involves altered expression of specific driver genes (e.g., SRC, STAT3, EDN1, CYP1A1, RHO, RELA).
• Enriched pathways, including the Wnt signaling pathway, are implicated in DHI's therapeutic effects on CTBH.