Untargeted metabolomics reveals the effect of MYH9 on the metabolism of vascular endothelial cells.

MYH9 plays a crucial role in vascular endothelial cells (VECs) and is a significant cause of abnormal bleeding in MYH9-related diseases (MYH9-RDs). However, research on how MYH9 regulates VECs has been limited so far, and there is a lack of biomarkers to assist in diagnosing MYH9-RD. In this study, we discovered that inhibiting MYH9 (via Blebbistatin, Bleb) or knocking down its gene significantly impairs angiogenesis, vasculogenesis, and VEC functions, including migration and tube formation. Further untargeted metabolomics identified 152 differential metabolites, such as sulfate and glycerophosphocholine, in MYH9-knockdown VECs, enriched in sulfur metabolism and glycerophospholipid metabolism. Importantly, MYH9 overexpression in VECs validated these key metabolites and pathways. These results reveal a close association between metabolites, such as sulfate and MYH9-RD vascular abnormalities, and provide potential diagnostic biomarkers and therapeutic targets for MYH9-RD.