To Explore the Mechanism of Atorvastatin Pre-intervention on Cocl2-induced Cardiomyocytes

Abstract

Background: Atorvastatin calcium, known for its anti-inflammatory and atherosclerotic plaque-stabilizing effects, is widely used for the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases, including coronary heart disease, angina pectoris, and cerebral infarction. Pyroptosis, a recently identified form of programmed cell death mediated by Caspase-1 and gasdermin D (GSDMD), is characterized by inflammasome activation and inflammatory cytokine release. Myocardial ischemia/reperfusion injury (MIRI) refers to exacerbated tissue damage that occurs when blood flow is restored (reperfusion) after a transient ischemic episode (insufficient blood supply). Pyroptosis has emerged as a central pathological mechanism in MIRI. In this study, we employed a rat MIRI model and an H9C2 cardiomyocyte hypoxia/reoxygenation (H/R) model to investigate the protective effects and underlying mechanisms of atorvastatin calcium pretreatment in both in vivo and in vitro systems.

Method: In vivo and in vitro models were established using ischemia/reperfusion (I/R) rats and cobalt chloride (CoCl₂)-induced hypoxia/reoxygenation (H/R) in H9C2 cells. Cell viability was measured via the CCK-8 assay. The expression levels of pyroptosis-related factors were assessed in both models through Western blotting, RT-qPCR, and immunohistochemical staining.

Result: Nucleotide-binding oligomerization domain (NOD)-like receptor signaling is an important pathway for mediating cardiac inflammation during myocardial I/R. In our experiments, Atorvastatin calcium pretreatment significantly ameliorates I/R-induced myocardial injury and H/R-induced pyroptosis, manifested by improved cardiac histopathology and cell viability. Western blot and RT-qPCR results showed that after pretreatment with atorvastatin calcium, atorvastatin calcium inhibited the expression of pro-inflammatory cytokines and pyro related molecules, including NLRP3, cleaved caspase-1, and GSDMD.

Conclusion: Our findings suggest that the NOD-like receptor signaling mediated inflammatory plays a pivotal role in myocardial I/R injury. After atorvastatin calcium pretreatment, inflammasome activation and pyroptosis are inhibited by the TLR4/Caspase-1/NLRP3 pathway, thus providing a potential strategy for the treatment of myocardial reperfusion injury.