Open AccessTherapeutic Potential of VIVIT, a Selective Peptide Inhibitor of Nuclear Factor of Activated T cells, in Cardiovascular Disorders
Author(s) -
Yu Haixiang,
Van Berkel Theo J.C.,
Biessen Erik A.L.
Publication year - 2007
Publication title -
cardiovascular drug reviews
Language(s) - English
Resource type - Journals
eISSN - 1527-3466
pISSN - 0897-5957
DOI - 10.1111/j.1527-3466.2007.00011.x
Subject(s) - nfat , calcineurin , pharmacology , phosphatase , angiogenesis , medicine , cancer research , chemistry , biochemistry , transplantation , enzyme
Cardiovascular disease is the major cause of death in industrialized nations. Targeted intervention in calcineurin, a calmodulin‐dependent, calcium‐activated phosphatase and its substrate, nuclear factor of activated T cells (NFAT), was demonstrated to be effective in the treatment of cardiovascular diseases. Although effective in the disruption of calcineurin phosphatase activity, cyclosporin A (CsA) and FK506 also resulted in undesired side effects and toxicity, prompting the discovery of VIVIT, a novel peptide inhibitor. VIVIT selectively and potently inhibits calcineurin/NFAT interaction, but does not compromise calcineurin phosphatase activity and non‐NFAT‐mediated signaling. VIVIT displays a favorable therapeutic profile as a potential drug candidate and constitutes a useful tool in exploring calcineurin‐NFAT functionality. This review describes the development of VIVIT peptide as a selective NFAT inhibitor and its application as a therapeutic agent in cardiovascular disorders including cardiac hypertrophy, restenosis, atherosclerosis, and angiogenesis.