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Updated: Aug 21, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Calpain-2 as a therapeutic target for sodium danshensu in mitigating myocardial ischaemia-reperfusion injury
Xiaolu Zhang1,2,3, Yujia Zheng3, Baolei Dou3
1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Background And Purpose:
Myocardial reperfusion, a life-saving intervention after heart attacks, paradoxically induces myocardial ischaemia-reperfusion injury (MIRI), a detrimental condition. MIRI is a persistent clinical challenge stemming from an incomplete understanding of its pathogenic mechanisms. This study aimed to identify the direct molecular target of sodium danshensu (SDSS) and elucidate the underlying mechanism by which it attenuates MIRI.
Experimental Approach:
We integrated in vivo (left anterior descending artery ligation and reperfusion model) and in vitro (hypoxia-reoxygenation model) approaches with proteomic profiling (HuProt™ microarray and liquid chromatography-tandem mass spectrometry [LC-MS/MS]), biophysical validation (cellular thermal shift assay [CETSA] and drug affinity responsive target stability [DARTS]) and molecular docking. The functional role of the identified target, calpain-2 (CAPN2) was further confirmed through pharmacological inhibition and genetic overexpression experiments.
Key Results:
SDSS administration significantly attenuated MIRI in in vivo and in vitro models. Using direct target-related technologies, CAPN2 was identified as a direct binding target of SDSS and was shown to be highly expressed in the heart. According to pathway enrichment analysis, CAPN2-mediated apoptosis in cardiomyocytes was a primary mechanism by which SDSS alleviated MIRI. The cardioprotective effects of SDSS were replicated by a selective CAPN2 inhibitor and abolished upon CAPN2 overexpression.
Conclusions And Implications:
SDSS confers cardioprotection by directly targeting and inhibiting CAPN2. This establishes CAPN2 as a potential therapeutic target for MIRI and provides a mechanistic basis for the development of SDSS-based therapies.
Insights
Sodium danshensu (SDSS) protects the heart by directly inhibiting calpain-2 (CAPN2), a key factor in myocardial ischaemia-reperfusion injury (MIRI). This finding offers a new therapeutic strategy for MIRI treatment.
Area of Science:
- Cardiovascular Research
- Molecular Pharmacology
- Biochemistry
Background:
- Myocardial ischaemia-reperfusion injury (MIRI) is a detrimental consequence of reperfusion therapy for heart attacks.
- The precise molecular mechanisms underlying MIRI remain incompletely understood, hindering effective treatment development.
Purpose of the Study:
- To identify the direct molecular target of sodium danshensu (SDSS).
- To elucidate the mechanism by which SDSS attenuates myocardial ischaemia-reperfusion injury (MIRI).
Main Methods:
- Integrated in vivo and in vitro models of MIRI.
- Proteomic profiling (HuProt™ microarray, LC-MS/MS) and biophysical validation (CETSA, DARTS).
- Functional confirmation via pharmacological inhibition and genetic manipulation of the identified target, calpain-2 (CAPN2).
Main Results:
- Sodium danshensu (SDSS) significantly reduced MIRI in experimental models.
- Calpain-2 (CAPN2) was identified as a direct binding target of SDSS and highly expressed in cardiac tissue.
- SDSS attenuated MIRI by inhibiting CAPN2-mediated apoptosis in cardiomyocytes, confirmed by selective inhibition and genetic overexpression studies.
Conclusions:
- Sodium danshensu (SDSS) exerts cardioprotection through direct inhibition of calpain-2 (CAPN2).
- Calpain-2 (CAPN2) is established as a potential therapeutic target for mitigating myocardial ischaemia-reperfusion injury (MIRI).
- This study provides a mechanistic foundation for developing SDSS-based therapies for MIRI.
