A further key advance is the experimental validation of a single nucleotide polymorphism that has genome wide significance in five vascular diseases and that significantly increases the amount of big endothelin-1 precursor in the plasma.
In the presence of significant uremia and absence of previously known association, the authors postulate that the sudden surge of uremia causes increase of endothelin-1 (a potent vasoconstrictor), resulting in downstream endothelin-induced vasculopathy with subsequent occlusion of the pre-capillary arteriolar network.
Endothelin-1 Expression Associated with Lipid Peroxidation and Nuclear Factor-κB Activation in Type 2 Diabetes Mellitus Patients with Angiopathy and Limb Amputation.