Related Experiment Video
Updated: Jan 6, 2026
Aggravation of Myocardial Ischemia upon Particulate Matter Exposure in Atherosclerosis Animal Model
Published on: December 10, 2021
TET3-Mediated m5C Modification of CCAT2 Accelerates Cardiac Microvascular Endothelial Cell Damage in Acute Coronary
Jun-Cheng Liu1,2,3, Wen-Juan Wang2,3, Ting-Ting Zhang3,4
1Department of Cardiology, Henan Province People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
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.
Insights
TET3 exacerbates acute coronary syndrome (ACS) by reducing CCAT2 stability and upregulating TRIM14, leading to cardiac microvascular endothelial cell damage. Silencing TET3 offers a potential therapeutic strategy for ACS.
Area of Science:
- Cardiovascular Biology
- Molecular Mechanisms of Disease
- Epigenetics
Background:
- Acute coronary syndrome (ACS) involves myocardial ischemia and cardiac microvascular endothelial cell (CMEC) damage.
- Identifying novel therapeutic targets for ACS is crucial.
Purpose of the Study:
- To investigate the role of TET3 in ACS-induced CMEC damage.
- To elucidate the molecular mechanism involving TET3, CCAT2, FUS, and TRIM14 in ACS.
- To explore TET3 as a potential therapeutic target for ACS.
Main Methods:
- Analysis of TET3 expression in ACS patients and healthy subjects.
- Stimulation of CMECs with ox-LDL and transfection with si-TET3.
- Assessment of cell proliferation, apoptosis, and angiogenesis.
- Evaluation of m5C modification, CCAT2 stability, and RNA-binding protein interactions (FUS, TRIM14).
Main Results:
- TET3 expression was elevated in ACS patients and ox-LDL-treated CMECs.
- Silencing TET3 protected CMECs from ox-LDL-induced damage.
- TET3 demethylated CCAT2, reducing its stability and expression.
- CCAT2 competed with TRIM14 for FUS binding, suppressing TRIM14 expression.
- CCAT2 knockdown or TRIM14 overexpression partially reversed the protective effects of si-TET3.
Conclusions:
- TET3 promotes ACS-induced CMEC damage by inhibiting CCAT2 expression and upregulating TRIM14 via FUS interaction.
- Targeting TET3 may represent a novel therapeutic approach for managing ACS.
Related Concept Videos
01:30Acute Coronary Syndrome I: Introduction
01:30Acute Coronary Syndrome III: Diagnostic Studies