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Dapagliflozin Ameliorates STZ-Induced Cardiac Hypertrophy in Type 2 Diabetic Rats by Inhibiting the Calpain-1
Lei Liu1, Haizhao Luo2, Yunyi Liang2
1The Second School of Clinical Medicine, Southern Medical University, Guangzhou City, Guangdong Province 510515, China.
Objective:
To investigate the effect of dapagliflozin (DAPA) on cardiac hypertrophy induced by type 2 diabetes mellitus (T2DM) and its mechanism.
Methods:
SD rats with T2DM were divided into a T2DM group (n = 6) and DAPA group (n = 6). They were, respectively, fed with the same amount of normal saline and 1 mg/kg DAPA. The control group (n = 6) was also fed with normal saline. The hearts were tested by the application of echocardiography and hemodynamics. Subsequently, fasting blood glucose (FBG), serum total cholesterol (TC), and triglyceride (TG) as well as interleukin- (IL-) 10, IL-6, and tumor necrosis factor (TNF)-α in serum were tested. H&E and Masson staining was performed to observe the degree of cardiac tissue lesions, and expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), calpain-1, p-IκBα, and p65 in myocardial tissue was tested by qRT-PCR and Western blot.
Results:
Compared with the control group, rats in the T2DM group exhibited significant diabetic symptoms: FBG was significantly elevated, and the levels of TC, TG, IL-6, and TNF-α were significantly increased, while the levels of IL-10 and the calpain activity were evidently decreased. However, DAPA treatment could improve the above changes. At the same time, the damage and fibrosis of the heart tissue in the DAPA group were markedly improved. Additionally, the mRNA expression of ANP and BNP in myocardial tissue of the DAPA group was markedly increased. And DAPA could inhibit the expression of p-IκBα/IκBα in the cytoplasm and p65 in the nucleus as well as the expression of calpain-1 in myocardial tissue.
Conclusion:
DAPA treatment ameliorates the cardiac hypertrophy caused by T2DM by decreasing body blood glucose, while reducing the expression of calpain-1 in cardiomyocytes and inhibiting the nuclear translocation of NF-κB.
Insights
Dapagliflozin (DAPA) effectively treats cardiac hypertrophy in type 2 diabetes mellitus (T2DM) by lowering blood glucose and reducing inflammation. DAPA also inhibits key proteins involved in cardiac remodeling and NF-κB signaling.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular complications, including cardiac hypertrophy.
- Diabetic cardiomyopathy is characterized by structural and functional changes in the heart, exacerbated by metabolic dysregulation and inflammation.
Purpose of the Study:
- To investigate the therapeutic effects of dapagliflozin (DAPA) on cardiac hypertrophy induced by T2DM.
- To elucidate the underlying molecular mechanisms of DAPA's action in a T2DM rat model.
Main Methods:
- Type 2 diabetes mellitus was induced in Sprague-Dawley rats, which were then treated with DAPA or saline.
- Cardiac function was assessed using echocardiography and hemodynamic measurements.
- Biochemical markers, inflammatory cytokines, and cardiac tissue markers (ANP, BNP, calpain-1, NF-κB pathway) were analyzed.
Main Results:
- DAPA treatment significantly improved diabetic symptoms, including elevated fasting blood glucose, total cholesterol, and triglycerides.
- DAPA reduced cardiac tissue damage and fibrosis, and normalized levels of inflammatory cytokines (IL-6, TNF-α) and IL-10.
- DAPA inhibited the expression of calpain-1 and suppressed the nuclear translocation of NF-κB (p-IκBα/IκBα and p65).
Conclusions:
- Dapagliflozin ameliorates cardiac hypertrophy in T2DM by improving glycemic control and reducing inflammation.
- DAPA exerts cardioprotective effects by decreasing calpain-1 expression and inhibiting NF-κB signaling in cardiomyocytes.
