Abstract
BackgroundDiabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction. The effective treatment strategy for DCM has not been developed.MethodsRats were divided into 3 groups with different treatment. The control group was only injected with citrate buffer (n = 8). The diabetes group and diabetes treated group were injected with streptozotocin to induce diabetes. After success of diabetes induction, the rats with diabetes were treated with (diabetes treated group, n = 8) or without (diabetes group, n = 8) recombinant human Neuregulin-1 (rhNRG-1). All studies were carried out 16 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate the cardiac function. Apoptotic cells were determined by TUNEL staining. Left ventricular (LV) sections were stained with Masson to investigate myocardial collagen contents. Related gene expressions were analyzed by quantitative real-time PCR (qRT-PCR).ResultsDiabetes impaired cardiac function manifested by reduced LV systolic pressure (LVSP), maximum rate of LV pressure rise and fall (+dp/dt max and -dp/dt max) and increased LV end-diastolic pressure (LVEDP). The rhNRG-1 treatment could significantly alleviate these symptoms and improve heart function. More TUNEL staining positive cells were observed in the diabetic group than that in the control group, and the rhNRG-1 treatment decreased apoptotic cells number. Furthermore, qRT-PCR assay demonstrated that rhNRG-1 treatment could decrease the expression of bax and caspase-3 and increase that of bcl-2. Collagen volume fraction was higher in the diabetic group than in the control group. Fibrotic and fibrotic related mRNA (type I and type III collagen) levels in the myocardium were significantly reduced by administration of rhNRG-1.ConclusionrhNRG-1 could significantly improve the heart function and reverse the cardiac remodeling of DCM rats with chronic heart failure. These results support the clinical possibility of applying rhNRG-1 as an optional therapeutic strategy for DCM treatment in the future.
Highlights
Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction
Twelve weeks after induction of diabetes, 16 diabetic rats remained in the experiment, which were randomly assigned to the following 2 groups: diabetic rats, and diabetic rats treated with recombinant human neuregulin1 (rhNRG-1) (10 μg/kg injected by tail vein every 2 day during the 2 weeks, n = 8; Novartis Pharmaceutical, Switzerland)
There was no significant difference in heart rate among the three groups
Summary
Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction. Many studies provided evidences for a specific cardiomyopathy in diabetes (diabetic cardiomyopathy, DCM), which may contribute to myocardial dysfunction in the absence of Neuregulin-1 (NRG-1) is a widely expressed signaling molecule that is involved in cell differentiation, proliferation, growth, survival, and apoptosis. It is encoded by a large gene (1400 Kb) located in chromosome 8p12, with several promoters and alternative splicing isoforms [7,8]. We decided to explore hemodynamic and physiopathological responses to recombinant human NRG-1 (beta isoform, rhNRG-1) in rat DCM model induced by STZ
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
