Multi-Omics and Network-Based Drug Repurposing for Septic Cardiomyopathy.
Summary
An integrated UPLC-MS/MS and RNA-seq approach with network proximity analysis nominated 14 FDA-approved candidates for septic cardiomyopathy. Acetaminophen and pyridoxal phosphate improved EF/FS and reduced BNP and cTnI in LPS-SCM mice, mediated by reduced prostaglandin synthesis and restored amino acid balance.
Key Findings
- Network proximity across multi-omics identified 129 drugs; 14 prioritized for ICU suitability and safety.
- Acetaminophen and pyridoxal phosphate improved EF and FS and decreased BNP and cTnI in LPS-induced SCM mice.
- Mechanistically, acetaminophen reduced prostaglandin synthesis/inflammation; pyridoxal phosphate restored amino acid balance.
Clinical Implications
Suggests repurposing acetaminophen and pyridoxal phosphate to mitigate septic cardiomyopathy, but clinical trials are needed before adoption given preclinical design and LPS model limitations.
Why It Matters
Provides a scalable, translational platform and identifies two ICU-accessible agents with mechanistic plausibility to protect the septic heart, potentially expediting clinical testing.
Limitations
- LPS-induced model may not capture polymicrobial/human SCM complexity
- Only two candidates were tested; no human data or safety endpoints in sepsis context
Future Directions
Prospective clinical trials to test dosing, safety, and efficacy in septic cardiomyopathy; expansion of the platform to polymicrobial and human tissue datasets.
Study Information
- Study Type
- Case-control
- Research Domain
- Treatment
- Evidence Level
- IV - Preclinical animal and cell-based experimental study with comparative groups (no human outcomes).
- Study Design
- OTHER