Circulating ACE2 levels and ACE I/D polymorphism in severe aortic stenosis.

Area of Science:

• Cardiovascular Medicine
• Genetics
• Biochemistry

Background:

• The renin-angiotensin system (RAS) plays a role in the fibro-calcific remodeling seen in aortic stenosis (AS).
• While increased angiotensin-converting enzyme 2 (ACE2) enzymatic activity is noted in severe AS, data on ACE2 protein levels and ACE genetic variations are limited.

Purpose of the Study:

• To investigate circulating concentrations of ACE2 and ACE in severe AS patients compared to controls.
• To examine the relationship between ACE2, ACE levels, and the ACE insertion/deletion (I/D) polymorphism in severe AS.
• To determine if these factors are independently associated with severe AS.

Main Methods:

• A cross-sectional case-control study involving 80 participants (40 severe AS, 40 controls).
• Measurements of circulating ACE and ACE2 concentrations using ELISA.
• Genotyping for the ACE I/D polymorphism (rs4340).
• Statistical analyses included multivariable logistic regression and Firth penalized regression.

Main Results:

• Circulating ACE2 concentrations were significantly higher in severe AS patients (median 1.9 ng/mL) versus controls (0.8 ng/mL).
• ACE levels were comparable between groups.
• ACE2 remained independently associated with severe AS (OR 1.48 per doubling).
• The ACE II genotype was independently associated with severe AS compared to the ID genotype.
• Neither ACE2 nor ACE I/D genotype correlated with stenosis severity or calcification.

Conclusions:

• Severe AS is associated with elevated circulating ACE2 concentrations and a differential ACE I/D genotype distribution, despite similar ACE levels.
• These findings suggest an altered systemic RAS balance in advanced valvular disease.
• Further validation in larger prospective cohorts is warranted.