Mechanosensitive Endothelial METTL7A Regulates Internal m 7 G mRNA Methylation and Protects Against Atherosclerosis
Authors' conclusion
METTL7A is a mechanosensitive internal m7G methyltransferase that maintains endothelial homeostasis by stabilizing the anti-inflammatory transcripts KLF4 (Krüppel-like factor 4) and NFKBIA (NFKB inhibitor alpha). Loss of METTL7A disrupts endothelial function and accelerates atherogenesis. Endothelial restoration of METTL7A through complementary targeted nanoparticle platforms significantly reduces atherosclerotic burden.
Study context
- Population
- Vascular endothelial cells under atheroprotective and atheroprone flow, human coronary arteries, and global and endothelial-specific Mettl7a1 knockout mice
Main finding
As reported in the abstract
- Atheroprotective unidirectional flow significantly induced METTL7A expression, promoting internal m7G methylation of endothelial transcripts without affecting cap-associated m7G
- METTL7A preferentially bound AG-enriched motifs in protein-coding mRNAs and increased internal m7G methylation and stability of KLF4 and NFKBIA transcripts
- Endothelial METTL7A expression significantly reduced by disturbed flow and in human atherosclerotic lesions
- Global or endothelial-specific loss of Mettl7a1 exacerbated atherosclerosis in mice independent of serum lipid levels
- Endothelial restoration of METTL7A by nanoparticle delivery (plasmid or N1-methylpseudouridine-modified mRNA) markedly attenuated atherosclerotic lesion formation in Mettl7a1-/- and ApoE-/- mice
Original publication
Mechanosensitive Endothelial METTL7A Regulates Internal m 7 G mRNA Methylation and Protects Against Atherosclerosis. Circulation. Published 11 August 2026. doi:10.
Summarised from the published abstract; every number is checked against it