B-Type Natriuretic Peptide: Endogenous Regulator of Myocardial Structure, Biomarker and Therapeutic Target

被引:27
|
作者
Ritchie, Rebecca H. [1 ]
Rosenkranz, Anke C. [2 ,3 ]
Kaye, David M. [1 ]
机构
[1] Baker IDI Heart & Diabet Inst, Heart Failure Res Grp, Melbourne, Vic 8008, Australia
[2] Uniklinikum Dusseldorf, Inst Pharmacol, Dusseldorf, Germany
[3] Uniklinikum Dusseldorf, Klin Pharmakol, Dusseldorf, Germany
关键词
BNP; cardiomyocyte; cyclic GMP; hypertrophy; natriuretic peptides; nesiritide; DEPENDENT PROTEIN-KINASE; SMOOTH-MUSCLE-CELLS; CONGESTIVE-HEART-FAILURE; GUANYLYL CYCLASE-A; CARDIAC MYOCYTE HYPERTROPHY; NITRIC-OXIDE SYNTHASE; INDUCED ENDOTHELIAL DYSFUNCTION; LEFT-VENTRICULAR HYPERTROPHY; RENIN-ANGIOTENSIN SYSTEM; RECEPTOR MESSENGER-RNAS;
D O I
10.2174/156652409789105499
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
B-type natriuretic peptide (BNP), initially identified in brain tissues, is now recognized as a key cardiac hormone. Numerous studies over the last decade have demonstrated that both exogenous and endogenous BNP prevent left ventricular (LV) hypertrophy in experimental settings, largely via activation of particulate guanylyl cyclase (pGC)-coupled receptors. BNP represents somewhat of a paradox, in that upregulation of BNP expression is widely used as a diagnostic marker for LV hypertrophy, diastolic dysfunction and heart failure in the clinic. We and others have postulated that BNP serves as an endogenous brake on the LV myocardium, seeking to curb the runaway train of signaling pathways that drive the progression from LV hypertrophy though remodeling, heart failure and death. This review summarizes the mechanisms of BNP's antihypertrophic actions, the role for cyclic GMP-mediated inhibition of pro-hypertrophic signaling, and BNP's impact on LV function. The improved understanding of the mechanisms of BNP regulation of LV hypertrophy and function that has emerged from both the experimental and clinical experience with this peptide provides new insight into the potential that BNP pharmacotherapy still offers for patients with LV hypertrophy.
引用
收藏
页码:814 / 825
页数:12
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