REST4-AAA Registry

Overview

This prospective observational study aims to investigate whether serum REST4 concentration can serve as a quantitative indicator correlated with abdominal aortic aneurysm (AAA) diameter and a predictive biomarker for AAA progression and rupture risk. Emerging evidence suggests that REST4, a splice variant of the RE-1 Silencing Transcription Factor (REST), is upregulated in vascular smooth muscle cells during AAA pathogenesis and may be released into circulation via exosomes. The study will enroll patients with asymptomatic AAA (diameter between 39-49 mm) and measure baseline serum REST4 levels, analyzing their association with morphological severity (maximum aortic diameter) and clinical outcomes (aneurysm growth rate, rupture and related mortality) through a 5-year follow-up period.

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.