McKie Paul M, Sangaralingham S Jeson, Burnett John C
Cardiorenal Research Laboratory, Division of Cardiovascular Disease, Mayo Clinic and Foundation, 200 First Street Southwest, Rochester, MN 55905, USA.
Curr Heart Fail Rep. 2010 Sep;7(3):93-9. doi: 10.1007/s11897-010-0016-6.
The natriuretic peptide (NP) family consists of structurally similar, although physiologically distinct, peptides that play an important role in cardiorenal homeostasis. CD-NP is a novel chimeric natriuretic peptide developed by the Mayo Clinic, in which the 15-amino acid COOH-terminus of dendroaspis NP is fused to C-type NP. CD-NP is a dual activator of NP receptors A and B, and therefore, possesses the strong antiproliferative and antifibrotic properties of C-type NP with the potent natriuretic, diuretic, and aldosterone-inhibiting properties of dendroaspis NP. CD-NP has favorable cardiorenal properties when compared to recombinant B-type NP (nesiritide), including preservation of glomerular filtration rate with minimal blood pressure-lowering effects. Thus, CD-NP has emerged as an appealing novel therapeutic strategy for heart failure. The endogenous NP system, the development rationale for CD-NP, as well as in vitro, animal, and human studies and future directions will be reviewed.
利钠肽(NP)家族由结构相似但生理功能不同的肽组成,这些肽在心脏肾脏稳态中起重要作用。CD-NP是梅奥诊所研发的一种新型嵌合利钠肽,其中树眼镜蛇利钠肽的15个氨基酸的羧基末端与C型利钠肽融合。CD-NP是NP受体A和B的双重激活剂,因此,它兼具C型利钠肽强大的抗增殖和抗纤维化特性以及树眼镜蛇利钠肽有效的利钠、利尿和抑制醛固酮特性。与重组B型利钠肽(奈西立肽)相比,CD-NP具有良好的心脏肾脏特性,包括在降压作用最小的情况下维持肾小球滤过率。因此,CD-NP已成为一种有吸引力的心力衰竭新型治疗策略。本文将综述内源性NP系统、CD-NP的研发原理以及体外、动物和人体研究及未来方向。