Journal
CARDIOVASCULAR DRUG REVIEWS
Volume 25, Issue 2, Pages 175-187Publisher
WILEY
DOI: 10.1111/j.1527-3466.2007.00011.x
Keywords
calcineurin; cardiovascular disorders; NFAT; VIVIT peptide
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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.
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