Mechanistic study of the effect of Endothelin SNPs in microvascular angina - Protocol of the PRIZE Endothelin...

Area of Science:

• Cardiology
• Pharmacogenomics
• Translational Medicine

Background:

• Microvascular angina, a cause of ischemia with non-obstructive coronary arteries (INOCA), has limited treatment options.
• Endothelin-1 (ET-1), a vasoconstrictor, plays a key role in microvascular angina pathophysiology.
• The PRIZE trial investigates Zibotentan, an endothelin receptor antagonist, for microvascular angina using a precision medicine approach based on the PHACTR1 G allele SNP.

Purpose of the Study:

• To genotype patients screened out of the PRIZE trial for genetic variants in the ET-1 pathway.
• To correlate these genotypes with phenotypic characteristics and microvascular function.
• To identify novel ET-1 genotypes for potential wider use of endothelin receptor antagonists.

Main Methods:

• Genotyping of patients screened out of the PRIZE trial for ET-1 pathway genetic variants.
• Correlation of genetic data with phenotypic characteristics (exercise tolerance, angina severity).
• Assessment of microvascular function using cardiovascular MRI and endothelin pathway signaling data.

Main Results:

• Identification of specific ET-1 pathway genotypes in patients with INOCA.
• Correlation between genetic variants and measures of angina severity and microvascular function.
• Establishment of a genotype-phenotype bio-resource for ET-1 pathway research.

Conclusions:

• The study will generate a comprehensive genotype-phenotype bio-resource.
• Novel ET-1 genotypes associated with microvascular angina will be identified.
• Findings will inform the potential expansion of endothelin receptor antagonist therapy for INOCA.