Endothelin-1 traps as a potential therapeutic tool: from diabetes to beyond?

Drug Discovery Today
Arjun JainJosef Flammer

Abstract

There is substantial research on the vasoactive peptide endothelin (ET)-1 in physiology, as well as in pathology. In fact, pathologically elevated levels of ET-1 have been found in several disease states, such as various cardiovascular diseases, different cancers, some neurodegenerative disorders, as well as in diabetes. Here, we describe and discuss ET-1, its importance in different diseases, and the potential therapeutic effects of ET-traps in the treatment of these diseases. Previous in vitro and in vivo research (in the diabetes disease space) demonstrated that ET-traps potently and significantly prevent the induction of different markers of diabetes-related pathology. This included induction of extracellular matrix (ECM) proteins (collagen 4α1 and fibronectin), which are pathologically elevated in diabetes. The ET-traps prevented induction of these and brought a significant return to non-diabetic levels. We also discuss the merits of using ET-traps over the currently used endothelin receptor antagonists (ERAs) and previously used therapeutic antibodies.

Citations

Mar 3, 2020·Clinical Hemorheology and Microcirculation·Sasa DragicPedja Kovacevic
Sep 22, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Claudia C BippesAlbert Neutzner

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