MYST1-Mediated Lysine Acetylation Stabilizes KLF4 to Promote Intimal Hyperplasia

Intimal hyperplasia is a key pathological process in cardiovascular diseases such as atherosclerosis and revascularization, and its molecular mechanism has not been fully elucidated. In this study, we investigated the role of acetyltransferase MYST1 in intimal hyperplasia after vascular injury and its molecular mechanism. The rat carotid artery injury model and in vitro smooth muscle cells (SMCs) culture experiments were used to knock down or overexpress MYST1 by lentiviral transfection. Histological staining, immunofluorescence, Western blot, and immunoprecipitation were used to detect vascular histopathological changes, protein expression and interactions. Vascular injury significantly upregulated MYST1 expression, and knockdown of MYST1 inhibited SMCs proliferation, migration and attenuated neointima formation. Mechanistic studies showed that MYST1 enhances protein stability and reduces ubiquitination degradation by mediating lysine acetylation modification of the transcription factor KLF4. Further studies revealed that KLF4 maintained the synthesis of SMCs by inhibiting the SRF-TAZ interaction. MYST1 regulates SMCs' phenotypic transformation through acetylation modification of KLF4, which is a key regulator of intimal hyperplasia, and provides a new target for combating vasoproliferative diseases.