Circulating ANGPTL2 Levels Increase in Humans and Mice Exhibiting Cardiac Dysfunction
Circulating ANGPTL2 Levels Increase in Humans and Mice Exhibiting Cardiac Dysfunction
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DOI：
10.1253/circj.cj-17-0327
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发表时间：
2018-02-01
影响因子：
3.3
通讯作者：
Oike, Yuichi
中科院分区：
文献类型：
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作者：
Tian, Zhe;Miyata, Keishi;Oike, Yuichi
背景资料：最近，据报道，从病理应激心脏分泌的血管生成素样蛋白2（ANGPTL 2）以自分泌/旁分泌方式加速心脏功能障碍，并且心脏中ANGPTL 2产生的抑制恢复了心脏功能和心肌能量代谢，从而阻断心力衰竭（HF）的发展。有趣的是，据报道HF患者的循环ANGPTL 2浓度增加，表明可能对心功能障碍有内分泌作用。然而，目前还不清楚为什么循环ANGPTL 2增加，在这些科目，以及是否循环ANGPTL 2改变心脏功能的内分泌manners.Methods和结果：它被发现，循环ANGPTL 2水平与左心房直径和肺毛细血管楔压呈正相关，并与扩张型心肌病患者的射血分数的百分比成反比。此外，在小鼠中，循环ANGPTL 2浓度随着横向主动脉缩窄（TAC）后HF的发展而增加，并且与缩短分数的百分比呈负相关。有趣的是，尽管循环ANGPTL 2浓度在过表达角化细胞衍生的ANGPTL 2的转基因小鼠中显著增加，但没有观察到病理性心脏重塑。此外，据观察，转基因小鼠和对照组之间的HF发展没有差异后TAC surgery.Conclusions：循环ANGPTL 2水平增加的主题经历心功能不全。然而，循环ANGPTL 2不会以内分泌方式促进心脏功能障碍，并且在HF期间观察到的循环ANGPTL 2水平增加是HF病理学中应激心脏的ANGPTL 2分泌增加的继发效应。
Background: Recently, it was reported that angiopoietin-like protein 2 (ANGPTL2) secreted from a pathologically stressed heart accelerates cardiac dysfunction in an autocrine/paracrine manner, and that suppression of ANGPTL2 production in the heart restored cardiac function and myocardial energy metabolism, thereby blocking heart failure (HF) development. Interestingly, circulating ANGPTL2 concentrations reportedly increase in HF patients, suggesting a possible endocrine effect on cardiac dysfunction. However, it remains unclear why circulating ANGPTL2 increases in those subjects and whether circulating ANGPTL2 alters cardiac function in an endocrine manner.Methods and Results: It was found that circulating ANGPTL2 levels are positively correlated with left atrial diameter and pulmonary capillary wedge pressure, and are inversely proportional to the percent of ejection fraction in patients with dilated cardiomyopathy. Furthermore, in mice, circulating ANGPTL2 concentrations increased as HF developed following transverse aorta constriction (TAC), and were inversely correlated with the percent of fractional shortening. Interestingly, although circulating ANGPTL2 concentrations significantly increased in transgenic mice overexpressing keratinocyte-derived ANGPTL2, no pathological cardiac remodeling was seen. Furthermore, it was observed that there was no difference in HF development between transgenic mice and controls following TAC surgery.Conclusions: Circulating ANGPTL2 levels increase in subjects experiencing cardiac dysfunction. However, circulating ANGPTL2 does not promote cardiac dysfunction in an endocrine manner, and increased levels of circulating ANGPTL2 seen during HF are a secondary effect of increased ANGPTL2 secretion from stressed hearts in HF pathologies.