REST4-AAA Registry

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by progressive dilation of the abdominal aorta, ultimately leading to catastrophic rupture with high mortality. Currently, clinical management relies mainly on aneurysm diameter for risk assessment, lacking reliable biomarkers to predict disease progression or rupture risk. Emerging evidence highlights the critical role of vascular smooth muscle cell (VSMC) phenotypic switching in AAA pathogenesis. Preliminary research has identified that RE-1 Silencing Transcription Factor (REST) in VSMC undergoes alternative splicing in AAA tissues, resulting in predominant expression of its splice variant REST4 and downregulation of full-length REST. This molecular shift triggers STAT1 activation, promoting synthetic VSMC transformation.

The study hypothesizes that synthetic VSMC in AAA lesions secrete REST4 into circulation via exosomes, making serum REST4 a potential dual-parameter biomarker that quantitatively correlates with aneurysm diameter (morphological severity) and predicts disease progression and rupture risk.

This prospective observational study will systematically evaluate asymptomatic AAA patients (39-49 mm diameter) to first determine the relationship between serum REST4 levels and maximum aortic diameter. Subsequently, through 5-year follow-up, the investigators will assess the prognostic capacity of serum REST4 concentration for predicting annual aneurysm growth rates, rupture incidence, and aneurysm-specific mortality.

Validation of correlation between serum REST4 concentration and AAA progression could transform current AAA surveillance approaches by integrating molecular profiling with traditional anatomical monitoring, enabling more precise risk stratification and personalized clinical management to ultimately improve patient outcomes.

Inclusion criteria

• Presence of an infrarenal AAA with a maximum diameter of 39-49 mm;
• Han nationality;
• Between 50 years or more, no gender limit;
• No mental illness;
• Subjects voluntarily participate in this study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion criteria

• Previous infrarenal aortic surgery;
• Planned major surgery;
• Known aortic dissection;
• Have received any other clinical trial treatment within 1 year;
• Systemic treatment with corticosteroids or other systemic immunomodulatory therapy;
• Severe infections, including but not limited to infections requiring hospitalization, bacteremia, severe pneumonia, etc.;
• Known or suspected inherited connective tissue disorder;
• Known or suspected prostate cancer;
• Calculated creatinine clearance of less than 30 ml/min;
• Known significant liver disease;
• Known human immunodeficiency virus infection at the time of screening；
• Serious concomitant illness associated with life expectancy of less than 2 years；
• Any other significant and unstable condition that could limit compliance with the trial protocol.