Furin convertase plays a critical role in the processing of proendothelin-1 to biologically active endothelin-1 in endothelial cells.
Furin inhibition may modulate ET-1 in endothelial cells; leaves open whether this extends to therapeutic targeting in cardiovascular disease.
Endothelin-1 (ET-1) is the most potent vasoactive peptide known to date. The peptide is initially synthesized as an inactive precursor (proET-1) which undergoes proteolysis at specific pairs of basic amino acids to yield bigET-1. Production of ET-1 then proceeds by cleavage of bigET-1 by the endothelin converting enzyme (ECE). Here, we demonstrate that the in vitro cleavage of proET-1 by furin, a mammalian convertase involved in precursor processing, produced bigET-1. Upon further processing, bigET-1 was converted to biologically active ET-1. Furthermore, we demonstrate that the furin inhibitor, decanoyl-Arg-Val-Lys-Arg chloromethylketone, abolished production of ET-1 in endothelial cells.
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Denault et al. (1995) studied this question.
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