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- W2311397788 abstract "Neuregulin-1 (NRG-1) 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 −/− ) 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 −/− mice were treated with vehicle, insulin, or recombinant human (rh)NRG-1 for 14 wk and were compared with nondiabetic apoE −/− littermates. Vehicle-treated diabetic apoE −/− 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. rhNRG-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." @default.
- W2311397788 created "2016-06-24" @default.
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- W2311397788 date "2016-04-01" @default.
- W2311397788 modified "2023-09-30" @default.
- W2311397788 title "Neuregulin-1 attenuates development of nephropathy in a type 1 diabetes mouse model with high cardiovascular risk" @default.
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- W2311397788 doi "https://doi.org/10.1152/ajpendo.00432.2015" @default.
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