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Published on: May 3, 2024
Tanshinone IIA reduces pyroptosis in rats with coronary microembolization by inhibiting the TLR4/MyD88/NF-κB/NLRP3
Hao-Liang Li1, Tao Li1, Zhi-Qing Chen1
1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascul.
Abstract:
Pyroptosis is an inflammatory form of programmed cell death that is linked with invading intracellular pathogens. Cardiac pyroptosis has a significant role in coronary microembolization (CME), thus causing myocardial injury. Tanshinone IIA (Tan IIA) has powerful cardioprotective effects. Hence, this study aimed to identify the effect of Tan IIA on CME and its underlying mechanism. Forty Sprague-Dawley (SD) rats were randomly grouped into sham, CME, CME + low-dose Tan IIA, and CME + high-dose Tan IIA groups. Except for the sham group, polyethylene microspheres (42 μm) were injected to establish the CME model. The Tan-L and Tan-H groups received intraperitoneal Tan IIA for 7 days before CME. After CME, cardiac function, myocardial histopathology, and serum myocardial injury markers were assessed. The expression of pyroptosis-associated molecules and TLR4/MyD88/NF-κB/NLRP3 cascade was evaluated by qRT-PCR, Western blotting, ELISA, and IHC. Relative to the sham group, CME group's cardiac functions were significantly reduced, with a high level of serum myocardial injury markers, and microinfarct area. Also, the levels of caspase-1 p20, GSDMD-N, IL-18, IL-1β, TLR4, MyD88, p-NF-κB p65, NLRP3, and ASC expression were increased. Relative to the CME group, the Tan-H and Tan-L groups had considerably improved cardiac functions, with a considerably low level of serum myocardial injury markers and microinfarct area. Tan IIA can reduce the levels of pyroptosis-associated mRNA and protein, which may be caused by inhibiting TLR4/MyD88/NF-κB/NLRP3 cascade. In conclusion, Tanshinone IIA can suppress cardiomyocyte pyroptosis probably through modulating the TLR4/MyD88/NF-κB/NLRP3 cascade, lowering cardiac dysfunction, and myocardial damage.
Insights
Tanshinone IIA (Tan IIA) protects the heart from injury caused by coronary microembolization (CME). It suppresses pyroptosis, a cell death process, by inhibiting the TLR4/MyD88/NF-κB/NLRP3 pathway, thus improving cardiac function.
Area of Science:
- Cardiovascular Research
- Cell Death Mechanisms
- Pharmacology
Background:
- Pyroptosis, an inflammatory programmed cell death, contributes to myocardial injury in coronary microembolization (CME).
- Tanshinone IIA (Tan IIA) exhibits known cardioprotective properties.
Purpose of the Study:
- To investigate the therapeutic effects of Tan IIA on CME-induced cardiac injury.
- To elucidate the underlying molecular mechanisms of Tan IIA's action, focusing on pyroptosis and related signaling pathways.
Main Methods:
- Coronary microembolization (CME) model established in Sprague-Dawley rats.
- Treatment groups included sham, CME, CME + low-dose Tan IIA, and CME + high-dose Tan IIA.
- Assessment of cardiac function, myocardial histopathology, serum injury markers, and expression of pyroptosis-related molecules and the TLR4/MyD88/NF-κB/NLRP3 pathway via qRT-PCR, Western blotting, ELISA, and IHC.
Main Results:
- CME significantly impaired cardiac function, increased myocardial injury markers, and elevated microinfarct size.
- CME induced increased expression of pyroptosis markers (caspase-1 p20, GSDMD-N, IL-18, IL-1β) and components of the TLR4/MyD88/NF-κB/NLRP3 cascade.
- Tan IIA treatment, particularly high-dose, significantly improved cardiac function, reduced injury markers and infarct size, and suppressed pyroptosis and TLR4/MyD88/NF-κB/NLRP3 pathway activation.
Conclusions:
- Tanshinone IIA effectively mitigates cardiac dysfunction and myocardial damage in a rat model of coronary microembolization.
- Tan IIA exerts its cardioprotective effects by suppressing cardiomyocyte pyroptosis.
- The mechanism involves the inhibition of the TLR4/MyD88/NF-κB/NLRP3 signaling cascade.
