The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic Peptide.
The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic Peptide.
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DOI：
10.1161/hypertensionaha.110.160796
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Burnett JC Jr
中科院分区：
文献类型：
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作者：
Sangaralingham SJ;Huntley BK;Martin FL;McKie PM;Bellavia D;Ichiki T;Harders GE;Chen HH;Burnett JC Jr
心肌老化的特征在于导致舒张和收缩功能障碍的LV纤维化。研究已经确定了C型利钠肽（CNP）的强效抗纤维化和抗增殖特性，但是循环CNP、LV纤维化和LV功能随自然衰老的相关变化之间的关系尚未确定。因此，我们在2、11和20月龄雄性Fischer大鼠中表征了血浆CNP与LV纤维化和功能的关系。此外，在体外，我们建立了CNP的抗增殖作用和清除受体的参与，使用成人心脏成纤维细胞。在此，我们首次确定循环CNP的进行性下降是自然衰老的特征，并与舒张和收缩功能受损之前LV纤维化的相互增加密切相关。此外，我们在培养的成人心脏成纤维细胞中证明，高剂量CNP的直接抗增殖作用可能涉及通过清除受体的非cGMP途径。总之，这些研究提供了新的见解心肌老化和抗纤维化和抗增殖肽CNP的关系。
Myocardial aging is characterized by LV fibrosis leading to diastolic and systolic dysfunction. Studies have established the potent anti-fibrotic and anti-proliferative properties of C-type natriuretic peptide (CNP), however the relationship between circulating CNP, LV fibrosis and associated changes in LV function with natural aging are undefined. Accordingly, we characterized the relationship of plasma CNP with LV fibrosis and function in 2, 11 and 20 month old male Fischer rats. Further in vitro, we establish the anti-proliferative actions of CNP and the participation of the clearance receptor using adult human cardiac fibroblasts. Here we establish for the first time that a progressive decline in circulating CNP characterizes natural aging and is strongly associated with a reciprocal increase in LV fibrosis which precedes impairment of diastolic and systolic function. Additionally we demonstrate in cultured adult human cardiac fibroblasts that the direct anti-proliferative actions of high dose CNP may involve a non-cGMP pathway via the clearance receptor. Taken together these studies provide new insights into myocardial aging and the relationship to the anti-fibrotic and anti-proliferative peptide CNP.