Neuregulin-1/ErbB signaling is impaired in the rat model of diabetic cardiomyopathy

Gui, Chun; Zhu, Ling; Hu, Ming; Lei, Lei; Long, Qicheng

doi:10.1016/j.carpath.2011.12.006

Cited by 46 publications

(31 citation statements)

References 33 publications

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“…In this study, systemic EGFR antagonism with AG1478 further aggravated I-R injury while EGFR agonism enhanced ischaemic tolerance. Others report reduced expression of ErbB2 and ErbB4 in rats with diabetic cardiomyopathy (Gui et al, 2012).…”

Section: Hypertrophy/heart Failurementioning

confidence: 98%

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Reichelt

O’Brien

Thomas

et al. 2017

The International Journal of Biochemistry & Cell Biology

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Section: Hypertrophy/heart Failurementioning

confidence: 98%

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Reichelt

O’Brien

Thomas

et al. 2017

The International Journal of Biochemistry & Cell Biology

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“…In animals, recombinant NRG-1 has beneficial effects on several forms of cardiomyopathy, including ischemic, toxic, viral, and diabetic cardiomyopathy (23,26). With specific relation to diabetes, endogenous NRG-1 signaling may be impaired in type 1 diabetic cardiomyopathy, while exogenous treatment with NRG-1 has reversed cardiac remodeling in diabetic rats (14,22,23,34). Currently, two forms of recombinant NRG-1 are being examined in clinical trials as potential therapies for heart failure with a reduced left ventricular (LV) ejection fraction (12,17).…”

mentioning

confidence: 99%

Neuregulin-1 attenuates development of nephropathy in a type 1 diabetes mouse model with high cardiovascular risk

Vandekerckhove

Vermeulen

Liu

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Vandekerckhove L, Vermeulen Z, Liu ZZ, Boimvaser S, Patzak A, Segers VF, De Keulenaer GW. Neuregulin-1 attenuates development of nephropathy in a type 1 diabetes mouse model with high cardiovascular risk. Am J Physiol Endocrinol Metab 310: E495-E504, 2016. First published January 19, 2016 doi:10.1152/ajpendo.00432.2015 is an endothelium-derived growth factor with cardioprotective and antiatherosclerotic properties and is currently being tested in clinical trials as a treatment for systolic heart failure. In clinical practice, heart failure often coexists with renal failure, sharing an overlapping pathophysiological background. In this study, we hypothesized that NRG-1 might protect against cardiomyopathy, atherosclerosis, and nephropathy within one disease process. We tested this hypothesis in a hypercholesterolemic apolipoprotein E-deficient (apoE Ϫ/Ϫ ) type 1 diabetes mouse model prone to the development of cardiomyopathy, atherosclerosis, and nephropathy and compared the effects of NRG-1 with insulin. Upon onset of hyperglycemia induced by streptozotocin, apoE Ϫ/Ϫ mice were treated with vehicle, insulin, or recombinant human (rh)NRG-1 for 14 wk and were compared with nondiabetic apoE Ϫ/Ϫ littermates. Vehicle-treated diabetic apoE Ϫ/Ϫ mice developed left ventricular (LV) dilatation and dysfunction, dense atherosclerotic plaques, and signs of nephropathy. Nephropathy was characterized by abnormalities including hyperfiltration, albuminuria, increased urinary neutrophil gelatinase-associated lipocalin (NGAL), upregulation of renal fibrotic markers, and glomerulosclerosis. rh-NRG-1 treatment induced systemic activation of ErbB2 and ErbB4 receptors in both heart and kidneys and prevented LV dilatation, improved LV contractile function, and reduced atherosclerotic plaque size. rhNRG-1 also significantly reduced albuminuria, NGALuria, glomerular fibrosis, and expression of fibrotic markers. Regarding the renal effects of rhNRG-1, further analysis showed that rhNRG-1 inhibited collagen synthesis of glomerular mesangial cells in vitro but did not affect AngII-induced vasoconstriction of glomerular arterioles. In conclusion, systemic administration of rhNRG-1 in hypercholesterolemic type 1 diabetic mice simultaneously protects against complications in the heart, arteries and kidneys.

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“…Our previous study showed NRG-1 protein expression and the phosphorylation of ErbB receptors are impaired in DCM [11]. The another study of us showed serum NRG-1β levels were positively correlated with serum VEGF and Ang-1 levels in patients with diabetes [12].…”

Section: Introductionmentioning

confidence: 99%

Neuregulin-1 Promotes Myocardial Angiogenesis in the Rat Model of Diabetic Cardiomyopathy

Gui

Zeng

Chen³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Microvascular insufficiency takes a critical role in the development of diabetic cardiomyopathy (DCM). So this study was designed to investigate the effects of Neuregulin-1 (NRG-1) treatment on myocardial angiogenesis and the changes of VEGF/Flk1 and Ang-1/Tie-2 signaling in the rat model of DCM. Methods: Diabetic rats were induced by a single intraperitoneal injection of Streptozotocin. 12 weeks after the diabetes induction, the rats with NRG-1 treatment were treated with tail vein injection of NRG-1 at the dose of 10µg/kg/d for consecutive 10 days. Cardiac function was assessed using catheter MPA cardiac function analysis system. Myocardial blood flow (MBF) was assessed with stable-isotope labeled microspheres. Capillary density was measured by CD31 immunohistochemistry. The protein expression and receptors phosphorylation were assessed using western blot. Results: Left ventricular function, capillary density and MBF were significantly reduced in DCM group when compared with those in the control group (P< 0.01, P< 0.01 and P< 0.05 respectively). Left ventricular function and capillary density were significantly increased in NRG-1 treatment group when compared with those in the DCM group (P< 0.05 and P< 0.05 respectively). The expression of VEGF and Ang-1 and the phosphorylation of Flk1 and Tie-1 were significantly decreased in DCM group as compared with those in the control group. However, those in the NRG-1 treatment group were significantly increased as compared with those in the DCM group. In vitro, NRG-1 treatment increased significantly the expression of VEGF and Ang-1 in human coronary artery smooth muscle cells. Conclusions: NRG-1 can increase the myocardial angiogenesis of DCM, probably via the direct effects of NRG-1 and via the increasing expression of VEGF and Ang-1. These findings may contribute to developing a novel approach to reverse the impaired angiogenic responses in diabetes or coronary artery disease.

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Neuregulin-1/ErbB signaling is impaired in the rat model of diabetic cardiomyopathy

Cited by 46 publications

References 33 publications

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Neuregulin-1 attenuates development of nephropathy in a type 1 diabetes mouse model with high cardiovascular risk

Neuregulin-1 Promotes Myocardial Angiogenesis in the Rat Model of Diabetic Cardiomyopathy

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