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Updated: Jul 28, 2025
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
CTRP5 Attenuates Doxorubicin-Induced Cardiotoxicity Via Inhibiting TLR4/NLRP3 Signaling
Zhaoxia Zhang1, Jianye Peng2,3, Yewen Hu1
1Department of Cardiology, The First Affiliated Hospital of Ningbo University, #59 Liuting Street, Haishu District, Ningbo, Zhejiang, China.
Background:
C1q/tumor necrosis factor-related protein 5 (CTRP5) has been reported to be a crucial regulator in cardiac ischemia/reperfusion (I/R) injury. Nevertheless, the potential role of CTRP5 in doxorubicin (DOX)-induced cardiotoxicity and the potential mechanisms remain largely unclear.
Methods:
We overexpressed CTRP5 in the hearts using an adeno-associated virus 9 (AAV9) system through tail vein injection. C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity for 4 weeks. Subsequently, cardiac staining and molecular biological analysis were performed to analyze the morphological and biochemical effects of CTRP5 on the cardiac injury. H9c2 cells were used for validation in vitro.
Results:
CTRP5 expression was down-regulated after DOX treatment both in vivo and in vitro. CTRP5 overexpression significantly attenuated DOX-induced cardiac injury, cardiac dysfunction, inhibited oxidative stress and inflammatory response. Mechanistically, CTRP5 overexpression markedly decreased the protein expression of toll-like receptor 4 (TLR4), NLRP3, cleaved caspase-1 and caspase-1, indicating TLR/NLRP3 signaling contributes to the cardioprotective role of CTRP5 in DOX-induced cardiotoxicity.
Conclusions:
Together, our findings demonstrated that CTRP5 overexpression could protect the heart from oxidative stress and inflammatory injury induced by DOX through inhibiting TLR4/NLRP3 signaling, suggesting that CTRP5 might be a potential therapeutic target in the prevention of DOX-induced cardiotoxicity.
Insights
C1q/tumor necrosis factor-related protein 5 (CTRP5) overexpression protects against doxorubicin (DOX)-induced cardiotoxicity by inhibiting oxidative stress and inflammation via the TLR4/NLRP3 pathway. This suggests CTRP5 as a potential therapeutic target for preventing DOX-induced heart damage.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pharmacology
Background:
- C1q/tumor necrosis factor-related protein 5 (CTRP5) is a known regulator of cardiac ischemia/reperfusion (I/R) injury.
- The role of CTRP5 in doxorubicin (DOX)-induced cardiotoxicity and its underlying mechanisms are not well understood.
Purpose of the Study:
- To investigate the protective effects of CTRP5 against DOX-induced cardiotoxicity.
- To elucidate the molecular mechanisms by which CTRP5 exerts its cardioprotective effects.
Main Methods:
- Overexpression of CTRP5 in mouse hearts using adeno-associated virus 9 (AAV9) via tail vein injection.
- Induction of DOX-induced cardiotoxicity in C57BL/6 mice and H9c2 cells.
- Cardiac staining and molecular biological analyses to assess injury, oxidative stress, and inflammation.
Main Results:
- CTRP5 expression was reduced by DOX treatment in vivo and in vitro.
- CTRP5 overexpression significantly attenuated DOX-induced cardiac injury, dysfunction, oxidative stress, and inflammation.
- CTRP5 overexpression decreased the expression of toll-like receptor 4 (TLR4), NLRP3, cleaved caspase-1, and caspase-1.
Conclusions:
- CTRP5 overexpression protects the heart from DOX-induced oxidative stress and inflammation.
- The protective effects are mediated through the inhibition of TLR4/NLRP3 signaling.
- CTRP5 represents a potential therapeutic target for preventing DOX-induced cardiotoxicity.
