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IP-MS methods for Protein interaction networks in the vasculature prioritize genes and pathways underlying coronary artery disease

ABSTRACT: Zhu QM, Hsu YH, Lassen FH, MacDonald BT, Stead S, Malolepsza E, Kim A, Li T, Mizoguchi T, Schenone M, Guzman G,Tanenbaum B, Fornelos N, Carr SA, Gupta RM, Ellinor PT, Lage K. Population-based association studies have identified many genetic risk loci for coronary artery disease (CAD), but it is often unclear how genes within these loci are linked to CAD. Here, we performed interaction proteomics for 11 CAD-risk genes to map their protein-protein interactions (PPIs) in human vascular cells and elucidate their biological relevance in CAD pathogenesis. The PPI networks contain many protein interactions that are outside of known biology in the vasculature and are enriched for genes involved in immunity-related and arterial-wall-specific mechanisms. Furthermore, several PPI networks derived from smooth muscle cells are significantly enriched for genetic variants associated with CAD and related vascular phenotypes. Finally, our networks identified 61 genes that are found in genetic loci associated with risk of CAD, prioritizing them as the causal candidates within these loci. Together, our results indicate that the PPI networks we have generated are a rich resource for guiding future research into the molecular pathogenesis of CAD.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000091699 | MassIVE | Wed Apr 12 14:43:00 BST 2023

REPOSITORIES: MassIVE

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