Role of hsa_circ_0000280 in regulating vascular smooth muscle cell function and attenuating neointimal hyperplasia...

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• RNA Biology

Background:

• Neointimal hyperplasia (NIH) in atherosclerosis involves pathological vascular smooth muscle cell proliferation.
• Circular RNAs (circRNAs) are implicated in cardiovascular diseases, but their role in vascular smooth muscle cell cycle regulation is unclear.
• Understanding circRNA function is crucial for developing new coronary heart disease (CHD) therapies.

Purpose of the Study:

• To identify the roles of circRNAs in vascular smooth muscle during CHD.
• To investigate the specific circRNA hsa_circ_0000280 and its mechanism in regulating vascular smooth muscle cell cycle.
• To explore the potential of hsa_circ_0000280 as a diagnostic or therapeutic target for CHD.

Main Methods:

• CircRNA sequencing of CHD patient samples.
• Human antigen R (ELAVL1) immunoprecipitation to identify interacting circRNAs.
• Gain/loss-of-function experiments in vitro and in vivo.
• Cell cycle analysis and assessment of neointimal thickness.

Main Results:

• hsa_circ_0000280 was identified as a CHD-associated circRNA that inhibits cell proliferation.
• hsa_circ_0000280 induces ELAVL1-dependent cell cycle arrest at the G1/S checkpoint.
• hsa_circ_0000280 facilitates the interaction between ELAVL1 and CDKN1A mRNA, stabilizing the complex and inhibiting NIH in vivo.
• Reduced neointimal thickness and smooth muscle cell proliferation were observed in vivo with hsa_circ_0000280 expression.

Conclusions:

• hsa_circ_0000280 inhibits vascular smooth muscle cell proliferation and NIH by regulating ELAVL1-mediated CDKN1A mRNA stabilization.
• This study reveals a novel regulatory pathway involving hsa_circ_0000280, ELAVL1, and CDKN1A in CHD.
• hsa_circ_0000280 represents a potential diagnostic biomarker and therapeutic target for CHD.