Genetic dysregulation of ET-1 and microvascular dysfunction

Disorders of coronary vasomotion include epicardial and/or microvascular coronary spasm, impaired coronary artery vasorelaxation and endothelial dysfunction-related reduced myocardial blood flow. Various vasoactive substances may be implicated.
Endothelin-1 (ET-1), a 21 amino acid peptide, is a potent vasoconstrictor which has long been implicated in the pathogenesis of vascular disease.
T. J. Ford et al. (British Heart Foundation, UK) performed a multimodality investigation into the role of ET-1 and this gene variant in the pathogenesis of coronary microvascular dysfunction in 391 patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease.
The G allele was associated with higher plasma serum ET-1. Patients with this allele had over double the odds of coronary microvascular dysfunction. The G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging and exercise testing.
Take-home message: Take-away message: ET-1 is a potent vasoconstrictor. Its newly identified polymorphic allele, and its receptors warrant future larger clinical trials to investigate the promise of ET-1 as a plausible therapeutic target for coronary microvascular dysfunction. These findings support the possibility of precision medicine in the future.