STAT3/miR-15a-5p/CX3CL1 Loop Regulates Proliferation and Migration of Vascular Endothelial Cells in Atherosclerosis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Atherosclerosis Research

Background:

• Vascular injury-induced endothelial cell proliferation contributes to atherosclerosis, the basis of coronary heart disease.
• The specific roles of Signal Transducer and Activator of Transcription 3 (STAT3) in microRNA regulation and endothelial dysfunction within atherosclerosis remain largely undefined.

Purpose of the Study:

• To elucidate the regulatory mechanism of STAT3 and microRNA-15a-5p (miR-15a-5p) in endothelial cell proliferation and their implications in atherosclerosis.

Main Methods:

• Investigated the interplay between STAT3, Interleukin-6 (IL-6), CX3CL1, and miR-15a-5p in endothelial cells.
• Assessed the impact of STAT3 activation and miR-15a-5p modulation on vascular endothelial cell proliferation and CX3CL1 expression.

Main Results:

• STAT3 activation by IL-6 upregulates CX3CL1 expression.
• miR-15a-5p inhibits both vascular endothelial cell proliferation and STAT3-mediated CX3CL1 transcription.
• A feedback loop exists where STAT3 positively regulates CX3CL1, which is then inhibited by miR-15a-5p, controlling endothelial cell proliferation.

Conclusions:

• miR-15a-5p plays a critical role in regulating endothelial cell proliferation by modulating the STAT3/CX3CL1 pathway.
• miR-15a-5p represents a promising therapeutic target for managing coronary atherosclerosis.