Yu Haixiang, van Berkel Theo J C, Biessen Erik A L
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, 2300 RA Leiden, The Netherlands.
Cardiovasc Drug Rev. 2007 Summer;25(2):175-87. doi: 10.1111/j.1527-3466.2007.00011.x.
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.
心血管疾病是工业化国家的主要死因。对钙调神经磷酸酶（一种钙调蛋白依赖性、钙激活的磷酸酶）及其底物活化T细胞核因子（NFAT）进行靶向干预已被证明对心血管疾病的治疗有效。尽管环孢素A（CsA）和FK506在破坏钙调神经磷酸酶的磷酸酶活性方面有效，但它们也会导致不良副作用和毒性，这促使人们发现了一种新型肽抑制剂VIVIT。VIVIT选择性且强效地抑制钙调神经磷酸酶/NFAT相互作用，但不损害钙调神经磷酸酶的磷酸酶活性和非NFAT介导的信号传导。作为一种潜在的候选药物，VIVIT显示出良好的治疗前景，并构成了探索钙调神经磷酸酶-NFAT功能的有用工具。本文综述了VIVIT肽作为一种选择性NFAT抑制剂的研发过程及其作为治疗剂在包括心肌肥大、再狭窄、动脉粥样硬化和血管生成在内的心血管疾病中的应用。
