Key result
Dapagliflozin reduces adverse cardiac remodeling and myocardial inflammation in experimental aortic stenosis.
Why the study?
Although SGLT2 inhibitors benefit heart failure with preserved and reduced ejection fraction, their influence in aortic stenosis-induced heart failure has not been established.
Does dapagliflozin attenuate cardiac remodeling and improve myocardial markers of inflammation and autophagy in rats with aortic stenosis?
Does dapagliflozin attenuate cardiac remodeling and improve myocardial markers of inflammation and autophagy in rats with aortic stenosis?
In a rat model of aortic stenosis, 12-week treatment with dapagliflozin attenuates cardiac remodeling, diastolic dysfunction, and myocardial inflammation independently of autophagic gene expression.
May attenuate remodeling and inflammation in experimental aortic stenosis; leaves open human translation and autophagy-independent mechanisms.
Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in the treatment of heart failure with both preserved and reduced ejection fraction. However, their influence in patients with aortic stenosis-induced heart failure has not been established. In this study, we investigated the effects of the SGLT2 inhibitor dapagliflozin on cardiac remodeling and myocardial markers of inflammation and autophagy in aortic stenosis rats. Methods Male Wistar rats were assigned into four groups: Sham (n=16); Sham treated with dapagliflozin (Sham-Dapa, n=15); aortic stenosis (AS, n=24); and AS treated with dapagliflozin (AS-Dapa, n=26) for 12 weeks. Aortic stenosis was induced by placing a 0.6-mm silver clip 3 mm distal to the aortic root. Cardiac structure and left ventricular (LV) function were assessed by echocardiogram. Inflammatory markers were analyzed using multiplex immunoassays and autophagy gene expression by real-time qPCR. Statistical analysis: ANOVA and Tukey or Dunn tests. Results Body weight was lower in Sham-Dapa and AS-Dapa than their controls. LV and atria weights were higher in AS and AS-Dapa than their controls and lower in AS-Dapa than AS. Ejection fraction did not differ between groups. Posterior wall shortening velocity was lower in AS and AS-Dapa than the controls. E/tissue Doppler imaging E’ was higher in AS than Sham and AS-Dapa (Table 1). Myocardial concentration of the cytokines IL-1β, IL-6, IL-10 and TNF-α was higher in AS than Sham and AS-Dapa. The expression of genes related to autophagy was not altered by dapagliflozin (Table 2). Conclusion Long-term dapagliflozin treatment attenuates cardiac remodeling and diastolic dysfunction and reduces the concentration of cytokines, independent of changes in the expression of autophagy-related genes in the heart of aortic stenosis rats.
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Rodrigues et al. (2026) studied Aortic stenosis-induced cardiac remodeling and heart failure (rat model) (n=81). Dapagliflozin vs. Untreated sham and untreated aortic stenosis control groups was evaluated on Cardiac remodeling (LV and atria weights, echocardiographic structure/function) and myocardial markers of inflammation and autophagy. Dapagliflozin for 12 weeks in aortic stenosis rats (n=81) lowered LV/atria weights, E/E' ratio, and myocardial IL-1β, IL-6, IL-10, and TNF-α without altering autophagy gene expression.
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