Neuregulin-1β Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium Handling
Background: Neuregulin (NRG-1), an essential stress-mediated paracrine growth factor, has a cardioprotective effect in failing heart. However, the underlying mechanism remains unclear. The role of NRG-1β in heart failure (HF) rats was examined.Methods and Results: Volume-overload HF rat model was cr...
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doaj-fc58dcd20d8145239c458c8e51d2ab322020-11-25T02:45:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-06-011010.3389/fphar.2019.00616440915Neuregulin-1β Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium HandlingXuehui Wang0Xiaozhen Zhuo1Jie Gao2Huibing Liu3Fei Lin4Aiqun Ma5Department of Cardiovascular Medicine, First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaDepartment of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Cardiovascular Medicine, First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaDepartment of Cardiovascular Medicine, First Affiliated Hospital of Xinxiang Medical University, Weihui, ChinaDepartment of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaBackground: Neuregulin (NRG-1), an essential stress-mediated paracrine growth factor, has a cardioprotective effect in failing heart. However, the underlying mechanism remains unclear. The role of NRG-1β in heart failure (HF) rats was examined.Methods and Results: Volume-overload HF rat model was created by aortocaval fistula surgery. The sham-operated (SO) rats received the same surgical intervention without the fistula. Thirty-five HF rats were injected with NRG-1β (NRG, 10 μg/kg·d) via the tail vein for 7 days, whereas 35 HF rats and 20 SO rats were injected with the same dose of saline. The echocardiographic findings showed left ventricular dilatation, systolic and diastolic dysfunction, and QTc interval prolongation in HF rats. The NRG-1β treatment attenuated the ventricular remodeling and shortened the QTc interval. Patch clamp recordings showed ICa-L was significantly decreased in the HF group, and NRG-1β treatment attenuated the decreased ICa-L. No significant differences in the kinetic properties of ICa-L were observed. The expressions of Cav1.2 and SERCA2a were significantly reduced, but the expression level of NCX1 was increased dramatically in the HF group. NRG-1β treatment could partially prevent the decrease of Cav1.2 and SERCA2a, and the increase of NCX1 in HF rats.Conclusions: NRG-1β could partly attenuate the heart function deterioration in the volume-overload model. Reduced function and expression of calcium transportation-related proteins might be the underlying mechanism.https://www.frontiersin.org/article/10.3389/fphar.2019.00616/fullheart failureneuregulin-1βL-type calcium channelcalcium handlingSERCA2a |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xuehui Wang Xiaozhen Zhuo Jie Gao Huibing Liu Fei Lin Aiqun Ma |
spellingShingle |
Xuehui Wang Xiaozhen Zhuo Jie Gao Huibing Liu Fei Lin Aiqun Ma Neuregulin-1β Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium Handling Frontiers in Pharmacology heart failure neuregulin-1β L-type calcium channel calcium handling SERCA2a |
author_facet |
Xuehui Wang Xiaozhen Zhuo Jie Gao Huibing Liu Fei Lin Aiqun Ma |
author_sort |
Xuehui Wang |
title |
Neuregulin-1β Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium Handling |
title_short |
Neuregulin-1β Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium Handling |
title_full |
Neuregulin-1β Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium Handling |
title_fullStr |
Neuregulin-1β Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium Handling |
title_full_unstemmed |
Neuregulin-1β Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium Handling |
title_sort |
neuregulin-1β partially improves cardiac function in volume-overload heart failure through regulation of abnormal calcium handling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-06-01 |
description |
Background: Neuregulin (NRG-1), an essential stress-mediated paracrine growth factor, has a cardioprotective effect in failing heart. However, the underlying mechanism remains unclear. The role of NRG-1β in heart failure (HF) rats was examined.Methods and Results: Volume-overload HF rat model was created by aortocaval fistula surgery. The sham-operated (SO) rats received the same surgical intervention without the fistula. Thirty-five HF rats were injected with NRG-1β (NRG, 10 μg/kg·d) via the tail vein for 7 days, whereas 35 HF rats and 20 SO rats were injected with the same dose of saline. The echocardiographic findings showed left ventricular dilatation, systolic and diastolic dysfunction, and QTc interval prolongation in HF rats. The NRG-1β treatment attenuated the ventricular remodeling and shortened the QTc interval. Patch clamp recordings showed ICa-L was significantly decreased in the HF group, and NRG-1β treatment attenuated the decreased ICa-L. No significant differences in the kinetic properties of ICa-L were observed. The expressions of Cav1.2 and SERCA2a were significantly reduced, but the expression level of NCX1 was increased dramatically in the HF group. NRG-1β treatment could partially prevent the decrease of Cav1.2 and SERCA2a, and the increase of NCX1 in HF rats.Conclusions: NRG-1β could partly attenuate the heart function deterioration in the volume-overload model. Reduced function and expression of calcium transportation-related proteins might be the underlying mechanism. |
topic |
heart failure neuregulin-1β L-type calcium channel calcium handling SERCA2a |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.00616/full |
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