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Therapeutic effects of neuregulin-1 in diabetic cardiomyopathy rats
Bingong Li1, Zeqi Zheng, Yunfeng Wei
1Department of Cardiology, First Affiliated Hospital, Nanchang University, Nanchang 330006, China. lbg2210@tom.com
Insights
Recombinant human Neuregulin-1 (rhNRG-1) effectively treats diabetic cardiomyopathy (DCM) in rats by improving heart function and reducing cardiac remodeling. This suggests rhNRG-1 may be a viable therapeutic option for DCM patients.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Diabetic cardiomyopathy (DCM) is a serious heart condition in diabetics, causing systolic and diastolic dysfunction.
- Current treatment strategies for DCM remain underdeveloped.
Purpose of the Study:
- To investigate the therapeutic potential of recombinant human Neuregulin-1 (rhNRG-1) in a rat model of diabetic cardiomyopathy.
- To evaluate the effects of rhNRG-1 on cardiac function, apoptosis, and myocardial fibrosis in diabetic rats.
Main Methods:
- Diabetes was induced in rats using streptozotocin.
- Rats were treated with or without rhNRG-1 for 16 weeks.
- Cardiac function was assessed via cardiac catheterization.
- Apoptosis and collagen content were analyzed using TUNEL and Masson staining, respectively.
- Gene expression of apoptosis-related and collagen-related factors was quantified using qRT-PCR.
Main Results:
- rhNRG-1 treatment significantly improved cardiac function, evidenced by better LV systolic pressure and reduced LV end-diastolic pressure.
- rhNRG-1 decreased apoptotic cell numbers and modulated the expression of apoptosis-related genes (bax, caspase-3, bcl-2).
- rhNRG-1 treatment reduced myocardial collagen content and fibrotic gene expression, mitigating cardiac remodeling.
Conclusions:
- rhNRG-1 demonstrates significant efficacy in improving heart function and reversing cardiac remodeling in DCM rats.
- These findings support the potential of rhNRG-1 as a future therapeutic strategy for diabetic cardiomyopathy.
Background:
Diabetic 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.
Methods:
Rats 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).
Results:
Diabetes 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.
Conclusion:
rhNRG-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.
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