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

American Journal of Physiology. Endocrinology and Metabolism
Leni VandekerckhoveGilles W De Keulenaer

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...Continue Reading

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Citations

Sep 7, 2016·Basic Research in Cardiology·Zarha VermeulenGilles W De Keulenaer
Mar 13, 2018·Cardiovascular Research·Hadis ShakeriVincent F Segers
Jul 21, 2017·American Journal of Physiology. Renal Physiology·Fenghua ZengRaymond C Harris
Oct 20, 2018·Clinical and Experimental Pharmacology & Physiology·Rui AdãoCarmen Brás-Silva
Apr 6, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Vincent F M SegersGilles W De Keulenaer
Nov 1, 2017·Hormone Molecular Biology and Clinical Investigation·Amitabha Ray
Oct 15, 2019·Circulation. Heart Failure·Gilles W De KeulenaerVincent F M Segers
Mar 29, 2020·Cellular Oncology (Dordrecht)·Vincent F M SegersGilles W De Keulenaer
Apr 13, 2019·Physiological Genomics·Zarha VermeulenVincent F M Segers
Jan 11, 2017·American Journal of Physiology. Renal Physiology·Christoffer LaustsenHans Stødkilde-Jørgensen
Aug 22, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Zarha VermeulenVincent F M Segers
Jan 21, 2021·Journal of the American Heart Association·Vincent F M Segers, Gilles W De Keulenaer
May 15, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Hadis ShakeriVincent F M Segers
Jul 13, 2021·Circulation. Heart Failure·Eline FeyenGilles W De Keulenaer

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