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Updated: Jun 17, 2025
Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR
Published on: April 8, 2013
Dapagliflozin alleviates right heart failure by promoting collagen degradation by reducing ROS levels
Dong-Dong Liu1, Xiao-Lin Liu1, Teng-Fei Zheng1
1National Key Laboratory for Innovation and Transformation of Luobing Theory, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China.
Background:
Right ventricular (RV) fibrosis is an important pathological change that occurs during the development of right heart failure (RHF) induced by pulmonary hypertension (PH). Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown to play a major role in left heart failure, but it is unclear whether it has a positive effect on RHF. This study aimed to clarify the effect of DAPA on PH-induced RHF and investigate the underlying mechanisms.
Methods:
We conducted experiments on two rat models with PH-induced RHF and cardiac fibroblasts (CFs) exposed to pathological mechanical stretch or transforming growth factor-beta (TGF-β) to investigate the effect of DAPA.
Results:
In vivo, DAPA could improve pulmonary hemodynamics and RV function. It also attenuated right heart hypertrophy and RV fibrosis. In vitro, DAPA reduced collagen expression by increasing the production of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). Additionally, DAPA was found to reduce reactive oxygen species (ROS) levels in CFs and the right heart in rats. Similar to DAPA, the ROS scavenger N-acetylcysteine (NAC) exerted antifibrotic effects on CFs. Therefore, we further investigated the mechanism by which DAPA promoted collagen degradation by reducing ROS levels.
Conclusions:
In summary, we concluded that DAPA ameliorated PH-induced structural and functional changes in the right heart by increasing collagen degradation. Our study provides new ideas for the possibility of using DAPA to treat RHF.
Insights
Dapagliflozin (DAPA) improves right heart function in pulmonary hypertension-induced right heart failure (RHF) by reducing fibrosis. This SGLT2 inhibitor works by increasing collagen degradation and reducing oxidative stress, offering a potential new treatment for RHF.
Area of Science:
- Cardiology
- Pharmacology
- Fibrosis Research
Background:
- Right ventricular (RV) fibrosis is a key factor in right heart failure (RHF) due to pulmonary hypertension (PH).
- The efficacy of Dapagliflozin (DAPA), an SGLT2 inhibitor, in RHF is not well-established, despite its known benefits in left heart failure.
Purpose of the Study:
- To investigate the therapeutic effects of DAPA on PH-induced RHF.
- To elucidate the underlying mechanisms by which DAPA may impact RHF.
Main Methods:
- Experiments were conducted on rat models of PH-induced RHF and in cardiac fibroblasts (CFs) subjected to mechanical stretch or TGF-β.
- DAPA's effects on pulmonary hemodynamics, RV function, hypertrophy, fibrosis, collagen expression, matrix metalloproteinases (MMP2, MMP9), and reactive oxygen species (ROS) were assessed.
Main Results:
- DAPA improved hemodynamics and RV function, while reducing hypertrophy and fibrosis in vivo.
- In vitro, DAPA decreased collagen by upregulating MMP2 and MMP9.
- DAPA reduced ROS levels in CFs and RV tissue, similar to the ROS scavenger N-acetylcysteine (NAC).
Conclusions:
- DAPA ameliorates PH-induced RHF by enhancing collagen degradation through a mechanism involving ROS reduction.
- The findings suggest DAPA as a potential therapeutic agent for treating RHF.
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