Therapeutic potential of VIVIT, a selective peptide inhibitor of nuclear factor of activated T cells, in cardiovascular disorders.
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.
Yu
Haixiang
H
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, 2300 RA Leiden, The Netherlands.
van Berkel
Theo J C
TJ
Biessen
Erik A L
EA
D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D006332:Cardiomegaly / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D006801:Humans; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D065095:Calcineurin Inhibitors; D050778:NFATC Transcription Factors; D009842:Oligopeptides; C121611:VIVIT peptide; D019703:Calcineurin