Related Experiment Video
Updated: Dec 31, 2025
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
Interleukin 35 ameliorates myocardial ischemia-reperfusion injury by activating the gp130-STAT3 axis
Xingdi Zhou1,2, Ni Xia1,2, Bingjie Lv1,2
1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Myocardial ischemia-reperfusion injury (MIRI) is common clinical complication, which represents significant challenge in the treatment of acute myocardial infarction (AMI) diseases. Interleukin 35 (IL-35) exhibits anti-inflammatory properties via the engagement of the gp130, IL-12Rβ2 and IL-27Rα receptors. However, whether IL-35 plays a beneficial role in the treatment of MIRI and potential underling mechanism are unclear. We showed that IL-35 conferred protection from MIRI as demonstrated by reduced infarct size and cardiac troponin T, improved cardiac function and decreased cardiomyocyte apoptosis in a mouse model. Despite activation of both STAT3 and STAT5 phosphorylation in the heart by IL-35, signal transducers and activators of transcription 3 (STAT3) was essential for mediating the IL-35-mediated protective effect on MIRI using cardiomyocyte-specific STAT3 deficient mice. Furthermore, gp130 was required for the STAT3 activation and cardio-protection induced by IL-35. Interestingly, IL-35 induced gp130 homodimer and gp130/IL-12Rβ2 heterodimers in cardiomyocyte. Our results indicate that IL-35 can execute a protective role against MIRI through a novel signaling pathway, IL-35-gp130-STAT3 pathway, in cardiomyocytes, which may be beneficial for the development of novel and effective therapeutic approaches to treat the MIRI.
Insights
Interleukin 35 (IL-35) protects against myocardial ischemia-reperfusion injury (MIRI) by activating the gp130-STAT3 pathway in heart cells. This finding offers a new therapeutic target for treating MIRI and acute myocardial infarction.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Myocardial ischemia-reperfusion injury (MIRI) is a critical complication of acute myocardial infarction (AMI).
- Interleukin 35 (IL-35) is known for its anti-inflammatory effects through specific receptor interactions.
- The role and mechanism of IL-35 in MIRI remain largely unexplored.
Purpose of the Study:
- To investigate the protective effects of IL-35 in a mouse model of MIRI.
- To elucidate the underlying molecular signaling pathways involved in IL-35's action on MIRI.
Main Methods:
- Utilized a mouse model to induce and study MIRI.
- Administered IL-35 and assessed cardiac function, infarct size, and cardiomyocyte apoptosis.
- Employed cardiomyocyte-specific STAT3-deficient mice to determine the role of STAT3.
- Analyzed receptor dimerization (gp130 homodimers and gp130/IL-12Rβ2 heterodimers) in cardiomyocytes.
Main Results:
- IL-35 treatment significantly reduced infarct size, cardiac troponin T levels, and cardiomyocyte apoptosis in MIRI mice.
- IL-35 improved overall cardiac function post-MIRI.
- STAT3 activation was crucial for IL-35's protective effects, while STAT5 phosphorylation was also observed.
- gp130 was essential for IL-35-induced STAT3 activation and cardioprotection, with IL-35 forming specific dimers with gp130.
Conclusions:
- IL-35 demonstrates significant cardioprotective effects against MIRI.
- The novel IL-35-gp130-STAT3 signaling pathway in cardiomyocytes mediates these protective effects.
- Targeting this pathway presents a promising therapeutic strategy for MIRI and related cardiovascular conditions.
Related Concept Videos
01:14Myocarditis III: Medical Management
01:20The JAK-STAT Signaling Pathway