Layer-specific Nos3 expression and genotypic distribution in bicuspid aortic valve aortopathy

Area of Science:

• Cardiovascular Biology
• Genetics
• Molecular Biology

Background:

• Bicuspid aortic valve (BAV) aortopathy is a complex condition.
• Understanding the molecular mechanisms underlying BAV aortopathy is crucial for developing targeted therapies.
• Nitric oxide synthase-3 (Nos3) plays a key role in vascular health.

Purpose of the Study:

• To investigate the relationship between Nos3 expression, activity, and genotype in patients with BAV-associated aortopathy.
• To compare these factors between BAV and tricuspid aortic valve (TAV) patients.
• To determine if tissue layer (intima-media vs. adventitia) influences Nos3 levels.

Main Methods:

• Gene expression analysis of Nos3 and Pecam1 in aortic tissue specimens.
• Measurement of NOS activity.
• Genotyping for Nos3 single-nucleotide polymorphisms (SNPs) -786T/C and 894G/T.
• Comparison between BAV and TAV patients with and without aneurysms.

Main Results:

• Elevated Nos3 expression was observed in the intima-media of BAV patients compared to TAV patients.
• Adventitial Nos3 expression was lower in aneurysmal aorta, irrespective of valve type.
• NOS activity was reduced in diseased adventitia.
• Aneurysmal BAV patients showed under-representation of the wild-type genotype for the -786T/C SNP, and cells with the C allele had lower Nos3 expression.

Conclusions:

• Differential Nos3 expression and activity in distinct aortic tissue layers are associated with BAV aortopathy and aneurysm formation.
• These findings suggest distinct pathophysiological mechanisms in BAV versus TAV ascending aortopathy.
• Nos3 genotype, particularly at the -786T/C locus, may influence Nos3 expression and contribute to BAV aortopathy.