Related Experiment Video
Updated: Apr 4, 2026
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Effects of atorvastatin on PDCD4/NF-κB/TNF-α signaling pathway during coronary microembolization of miniature pigs
1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Objective:
In this study, we explore the effects of pretreatment with atorvastatin on the cardiac function of piglets after coronary microembolization (CME).
Methods:
Twenty Bama miniature pigs were randomized to sham surgery group (sham group), CME Group, conventional dose group and intensive-dose group, with 5 miniature pigs in each group. Pigs in the CME group received a total dosage of 100,000 microspheres (42 μm) suspended in 10 ml normal saline within 40 min, while animals in the sham group received the same dosage of normal saline. In the conventional dose group, atorvastatin (1.5mg/kg) was given once daily starting 7d before microembolization. In the intensive-dose group, atorvastatin (1.5mg/kg) was also given once daily 7d before intervention, and an additional 3mg/kg 4h before percutaneous coronary intervention. Cardiac function indices were determined by echocardiography; and infarct size was determined histopathologically. PDCD4 mRNA and TNF-α mRNA and protein expression were evaluated by quantitative fluorescence-polymerase chain reaction and Western blot, respectively. NF-κB activation was evaluated by electrophoretic mobility shift assay.
Results:
(1) Cardiac function was significantly lower (P<0.05) in CME group compared with the sham group. CME reduced myocardial systolic dysfunction and left ventricular dilatation. The conventional and intensive-dose groups showed improved CME-induced cardiac function when compared with the CME Group (P<0.05). (2) Compared with the conventional group, the dose-intensive group showed lower PDCD4 and TNF-α expression and NF-κB activation as well as improved cardiac function (P<0.05).
Conclusions:
Atorvastatin effectively improved CME-induced cardiac damage with intensive-dose therapy showing better outcome. The protective effects are mediated via suppression of PDCD4/NF-κB/TNF-α signaling in cardiomyocytes.
Insights
Atorvastatin pretreatment improved cardiac function after coronary microembolization (CME) in piglets. Intensive dosing offered superior protection by suppressing PDCD4/NF-κB/TNF-α signaling.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Coronary microembolization (CME) causes significant cardiac dysfunction.
- Statins, like atorvastatin, are known for their pleiotropic effects beyond lipid-lowering.
- Investigating atorvastatin's protective mechanisms in CME models is crucial for therapeutic development.
Purpose of the Study:
- To evaluate the efficacy of atorvastatin pretreatment in mitigating cardiac damage induced by CME.
- To compare the effects of conventional versus intensive dosing regimens of atorvastatin.
- To elucidate the molecular pathways involved in atorvastatin's cardioprotective effects.
Main Methods:
- A piglet model of coronary microembolization (CME) was established.
- Animals were randomized into sham, CME, conventional-dose atorvastatin, and intensive-dose atorvastatin groups.
- Cardiac function was assessed via echocardiography, infarct size via histopathology, and molecular markers (PDCD4, TNF-α, NF-κB) via qPCR, Western blot, and EMSA.
Main Results:
- CME significantly impaired cardiac function and induced myocardial damage.
- Both conventional and intensive atorvastatin doses improved cardiac function compared to the CME group.
- The intensive-dose group exhibited superior outcomes, with reduced PDCD4, TNF-α expression, and NF-κB activation.
Conclusions:
- Atorvastatin pretreatment effectively protects against CME-induced cardiac damage in piglets.
- An intensive dosing strategy of atorvastatin yields better cardioprotective results.
- The protective mechanism involves the suppression of the PDCD4/NF-κB/TNF-α signaling pathway in cardiomyocytes.
