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Updated: Apr 20, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Atorvastatin at reperfusion reduces myocardial infarct size in mice by activating eNOS in bone marrow-derived cells
Yikui Tian1, Joel Linden2, Brent A French3
1Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, United States of America; Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin, P.R. China.
Background:
The current study was designed to test our hypothesis that atorvastatin could reduce infarct size in intact mice by activating eNOS, specifically the eNOS in bone marrow-derived cells. C57BL/6J mice (B6) and congenic eNOS knockout (KO) mice underwent 45 min LAD occlusion and 60 min reperfusion. Chimeric mice, created by bone marrow transplantation between B6 and eNOS KO mice, underwent 40 min LAD occlusion and 60 min reperfusion. Mice were treated either with vehicle or atorvastatin in 5% ethanol at a dose of 10 mg/kg IV 5 min before initiating reperfusion. Infarct size was evaluated by TTC and Phthalo blue staining.
Results:
Atorvastatin treatment reduced infarct size in B6 mice by 19% (p<0.05). In eNOS KO vehicle-control mice, infarct size was comparable to that of B6 vehicle-control mice (p = NS). Atorvastatin treatment had no effect on infarct size in eNOS KO mice (p = NS). In chimeras, atorvastatin significantly reduced infarct size in B6/B6 (donor/recipient) mice and B6/KO mice (p<0.05), but not in KO/KO mice or KO/B6 mice (p = NS).
Conclusions:
The results demonstrate that acute administration of atorvastatin significantly reduces myocardial ischemia/reperfusion injury in an eNOS-dependent manner, probably through the post-transcriptional activation of eNOS in bone marrow-derived cells.
Insights
Atorvastatin reduced heart attack size in mice by activating endothelial nitric oxide synthase (eNOS), particularly in bone marrow-derived cells. This protective effect was dependent on eNOS function.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cell Biology
Background:
- Myocardial ischemia/reperfusion (I/R) injury is a significant clinical concern.
- Statins, like atorvastatin, are known for their lipid-lowering effects.
- The specific mechanisms by which atorvastatin might protect against I/R injury are under investigation.
Purpose of the Study:
- To test the hypothesis that atorvastatin reduces infarct size by activating endothelial nitric oxide synthase (eNOS).
- To determine if this effect is mediated by eNOS in bone marrow-derived cells.
Main Methods:
- Utilized C57BL/6J (B6) and eNOS knockout (KO) mice.
- Created chimeric mice via bone marrow transplantation between B6 and eNOS KO mice.
- Administered atorvastatin or vehicle before reperfusion following LAD occlusion and evaluated infarct size.
Main Results:
- Atorvastatin reduced infarct size by 19% in B6 mice.
- No significant reduction in infarct size was observed in eNOS KO mice treated with atorvastatin.
- Atorvastatin reduced infarct size in B6/B6 and B6/KO chimeras, but not in KO/KO or KO/B6 chimeras.
Conclusions:
- Acute atorvastatin administration significantly reduces myocardial I/R injury.
- The protective effect is dependent on eNOS.
- The mechanism likely involves post-transcriptional activation of eNOS in bone marrow-derived cells.
