CCCTC-binding factor suppresses alpha-2-macroglobulin transcription to improve vascular endothelial cell functions in...

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Endothelial Cell Function

Background:

• Vascular endothelial cell dysfunction is central to lower extremity arteriosclerosis obliterans (LEASO).
• Alpha-2-macroglobulin (A2M) and CCCTC-binding factor (CTCF) are implicated in endothelial cell function relevant to LEASO.

Purpose of the Study:

• To elucidate the role of CTCF in regulating vascular endothelial cell function in LEASO.
• To investigate the mechanism by which CTCF influences A2M in the context of LEASO.

Main Methods:

• Establishment of rat models for LEASO and in vitro LEASO cell models using HUVECs.
• Assessment of vascular parameters (intima-media ratio, lumen diameter), blood lipids, and inflammatory markers.
• Analysis of cell viability, apoptosis, and autophagy-related proteins (LC3II/I, p62), alongside CTCF and A2M expression.
• Verification of CTCF's transcriptional regulation on A2M and experimental manipulation using sh-A2M and CTCF overexpression.

Main Results:

• LEASO rat models exhibited arterial narrowing, endothelial disorder, dyslipidemia, elevated inflammatory factors, high A2M, and low CTCF expression.
• In vitro, ox-LDL-treated HUVECs showed reduced viability, increased apoptosis, and impaired autophagy, effects reversed by A2M knockdown.
• CTCF overexpression in HUVECs inhibited A2M transcription, enhanced cell viability and autophagy, and reduced apoptosis.

Conclusions:

• CCCTC-binding factor (CTCF) plays a protective role in vascular endothelial cells affected by lower extremity arteriosclerosis obliterans (LEASO).
• CTCF exerts its beneficial effects by transcriptionally inhibiting alpha-2-macroglobulin (A2M).
• Targeting the CTCF-A2M pathway presents a potential therapeutic strategy for managing LEASO.