<scp>TET3</scp> ‐Mediated <scp>m5C</scp> Modification of <scp>CCAT2</scp> Accelerates Cardiac Microvascular Endothelial Cell Damage in Acute Coronary Syndrome

Acute coronary syndrome (ACS) is a clinical syndrome involving myocardial ischemia. This study aimed to elucidate the mechanism of TET3 in ACS-induced CMEC damage, thereby identifying a new target for ACS treatment. The expression of TET3 in ACS patients and healthy subjects was analyzed. CMECs were stimulated with ox-LDL and transfected with si-TET3 for the detection of TET3 RNA and protein levels. Cell proliferation, apoptosis, and angiogenesis were evaluated. Subsequently, m5C modification and TET3 enrichment on CCAT2 were assessed, and CCAT2 stability was measured. The binding relationships between CCAT2 and FUS and between FUS and TRIM14 mRNA were analyzed. Additionally, lncRNA CCAT2 inhibition or TRIM14 overexpression in combination with si-TET3 treatment was conducted to verify the underlying mechanism. TET3 was strongly expressed in serum from ACS patients and ox-LDL-stimulated CMECs, and silencing TET3 reduced ox-LDL-induced CMEC damage. TET3 removed m5C modification on CCAT2 to decrease CCAT2 stability and expression. With TRIM14, CCAT2 competes to bind to FUS to suppress TRIM14 expression. CCAT2 knockdown or TRIM14 overexpression partially reversed the protective effect of si-TET3 on CMEC damage. In conclusion, TET3 removed m5C modification to inhibit CCAT2 expression and reduced the binding relationship between CCAT2 and FUS to upregulate TRIM14, thereby exacerbating CMEC damage in ACS.