OBJECTIVES: CD4CD25 regulatory T cells (Tregs) play a key role in the prevention 
of various inflammatory and autoimmune disorders by suppressing immune 
responses. The beneficial effect of statins on myocardial ischemia-reperfusion 
injury (IRI) depends in part on their immunomodulatory and anti-inflammatory 
mechanisms. We aimed to determine whether Tregs contribute to statin-induced 
cardioprotection against myocardial IRI.
METHODS: Thirty-two rats were divided into four groups: sham, 
ischemia-reperfusion (IR), rosuvastatin (RSV)/IR, and mevalonic acid 
(MVA)+RSV/IR. Myocardial IR was induced by a 30-min coronary occlusion, followed 
by a 48-h reperfusion. RSV (5 mg/kg) was administered intravenously 18 h before 
IR. The rats were killed after 48-h reperfusion. Serum cardiac troponin I (cTnI) 
was measured by ELISA, infiltration of inflammatory cells in myocardium by 
hematoxylin and eosin staining, expression of FoxP3 protein by western blotting, 
accumulation of Tregs in myocardium by immunohistochemical examination, and 
infarct size by TTC staining.
RESULTS: Significant elevation in serum cTnI, enlarged infarct size, and marked 
infiltration of inflammatory cells in myocardium were observed in the IR group. 
The administration of RSV significantly reduced the serum cTnI level, attenuated 
the accumulation of inflammatory cells, decreased infarct size, and increased 
the FoxP3 expression and Treg accumulation in myocardium compared with the IR 
group. The combination of RSV and MVA pretreatment partially abolished the 
anti-inflammatory and infarct size-limiting effects and completely reversed Treg 
accumulation in myocardium induced by RSV. The accumulation of inflammatory 
cells was negatively correlated with FoxP3 expression and Treg accumulation in 
the ischemic myocardium.
CONCLUSION: RSV pretreatment was associated with more Treg accumulation, less 
inflammatory response, and myocardial injury, suggesting that such 
cardioprotection against IRI was partially mediated by Treg-negative modulation 
of inflammation response, probably through the HMG-CoA reductase pathway.