Angiogenic gene networks are dysregulated in opioid use disorder: evidence from multi-omics and imaging of postmortem human brain

Emily F. Mendez, Haichao Wei, Ruifeng Hu, Laura Stertz, Gabriel R. Fries, Xizi Wu, Katherine E. Najera, Michael D. Monterey, Christie M. Lincoln, Joo won Kim, Karla Moriel, Thomas D. Meyer, Sudhakar Selvaraj, Antonio L. Teixeira, Zhongming Zhao, Junqian Xu, Jiaqian Wu, Consuelo Walss-bass

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Opioid use disorder (OUD) is a public health crisis in the U.S. that causes over 50 thousand deaths annually due to overdose. Using next-generation RNA sequencing and proteomics techniques, we identified 394 differentially expressed (DE) coding and long noncoding (lnc) RNAs as well as 213 DE proteins in Brodmann Area 9 of OUD subjects. The RNA and protein changes converged on pro-angiogenic gene networks and cytokine signaling pathways. Four genes (LGALS3, SLC2A1, PCLD1, and VAMP1) were dysregulated in both RNA and protein. Dissecting these DE genes and networks, we found cell type-specific effects with enrichment in astrocyte, endothelial, and microglia correlated genes. Weighted-genome correlation network analysis (WGCNA) revealed cell-type correlated networks including an astrocytic/endothelial/microglia network involved in angiogenic cytokine signaling as well as a neuronal network involved in synaptic vesicle formation. In addition, using ex vivo magnetic resonance imaging, we identified increased vascularization in postmortem brains from a subset of subjects with OUD. This is the first study integrating dysregulation of angiogenic gene networks in OUD with qualitative imaging evidence of hypervascularization in postmortem brain. Understanding the neurovascular effects of OUD is critical in this time of widespread opioid use.

Original languageEnglish (US)
Pages (from-to)7803-7812
Number of pages10
JournalMolecular psychiatry
Issue number12
StatePublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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