Aortic & peripheral vascular disease
Histone Lactylation–Mediated Metabolic Remodeling in Vascular Smooth Muscle Cells Aggravates Aortic Aneurysm and Dissection by Promoting Lactate Accumulation
An erratum to this article was published (Circulation, 3 Mar 2026 ↗)
Authors' conclusion
Histone lactylation changes the metabolism and phenotype of VSMC in AAD.
Study context
- Population
- Patients with aortic aneurysm and murine model of aneurysm and dissection (AAD); Vascular smooth muscle cells (VSMCs) treated with angiotensin II
- Comparison
- Patients with aortic aneurysm vs controls; Pdk1 or Kat7 inhibition in mice
Methodological detailshuman aortic tissue, murine AAD model, VSMC-specific Pdk1 or Kat7 knockout mice, pharmacological inhibition
- Human aortic tissue
- Murine AAD model
- VSMC-specific Pdk1 or Kat7 knockout mice
- Pharmacological inhibition
Main finding
As reported in the abstract
- Histone lactylation (H4K16 lactylation (H4K16la)) increased in aortic tissues of patients with AAD and mice
- Enhanced histone lactylation linked to increased PDK1 transcription, accelerating lactate production in VSMCs
- Positive feedback loop of H4K16la, PDK1 and lactate alters VSMC metabolism and phenotype
- KAT7 is a histone lactyltransferase in VSMCs
- Genetic or pharmacological inhibition of PDK1 or KAT7 decreased AAD injury by disrupting the H4K16la/PDK1/lactate pathway
- Patients with AAD have elevated blood and aortic lactate and elevated aortic H4K16la vs controls
Original publication
Histone Lactylation–Mediated Metabolic Remodeling in Vascular Smooth Muscle Cells Aggravates Aortic Aneurysm and Dissection by Promoting Lactate Accumulation. Circulation. Published 5 January 2026. doi:10.
Summarised from the published abstract; every number is checked against it