Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy
Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy
复制标题
DOI：
10.1177/0192623316634231
复制
发表时间：
2017-02-01
影响因子：
1.5
通讯作者：
Colton, Heidi M.
中科院分区：
文献类型：
--
作者：
Dunn, Michael E.;Manfredi, Thomas G.;Colton, Heidi M.
鉴于利钠肽作为人类心血管失调和功能障碍的血清生物标志物的实用性，以及心房利钠肽的高度跨物种序列保守性，利钠肽有潜力在药物开发的多个阶段作为鉴定心脏毒性化合物的翻译生物标志物。本研究评估并比较了大鼠在长期游泳或每日口服过氧化物酶体增殖物激活受体激动剂后，运动诱导和药物诱导的心脏质量增加时，n -末端心房钠肽（NT-proANP）和n -末端脑钠肽（NT-proBNP）的反应。8 ~ 10周龄雄性Sprague-Dawley大鼠分为对照组、主动对照组、游泳组和药物性心肌肥厚组。在给药28天后，游泳组和药物性心肌肥厚组的相对心脏重量均增加了15%，血清NT-proANP和NT-proBNP值仅与复合给药引起的心肌肥厚相关。血清利钠肽浓度在28天游泳方案诱导的适应性生生性心肌肥厚反应中没有变化。这些数据支持使用利钠肽作为区分生理性和药物性心脏肥大的液体生物标志物。
Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.