Simvastatin attenuates cardiac isograft ischemia-reperfusion injury by down-regulating CC chemokine receptor-2 expression
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Updated: Jul 12, 2026
Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Rong Yin1, Jiaquan Zhu, Zhongqiu Wang
1Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, China.
Objective:
Accumulating evidence reveals that statins possess direct anti-inflammatory properties through inhibition of proinflammatory cytokine and chemokine secretion in addition to their antioxidant effects, which may contribute to amelioration of ischemia-reperfusion injury. This study tested the hypothesis that perioperative treatment of simvastatin suppresses the cardiac isograft ischemia-reperfusion injury by down-regulation of CC chemokine receptor-2 expression in an inbred rat model of cardiac transplantation.
Methods:
Donor hearts from Lewis rats were heterotopically transplanted to Lewis rat recipients. Recipients were orally treated with simvastatin (1 mg/kg) or vehicle every morning 3 days before the surgery until the harvest day. Rats were killed at 6 hours and at 1, 3, and 7 days after transplantation. Injury was assessed by infarct size measurement, histologic and immunohistochemical examination, and intragraft myeloperoxidase activity assay. Monocyte chemoattractant protein-1 levels in serum and graft were analyzed by enzyme-linked immunosorbent assay, and intragraft CC chemokine receptor-2 expression was measured by quantitative real-time polymerase chain reaction.
Results:
The infarct size and macrophage infiltration were all significantly reduced in the simvastatin-treated group compared with those of the control group at 1 day after transplantation. Neutrophil accumulation was significantly suppressed until 3 days after transplantation, whereas myeloperoxidase activity had been significantly diminished at 1 day after transplantation. Both monocyte chemoattractant protein-1 concentrations in serum and graft were remarkably decreased at 6 hours after transplantation. Intragraft CC chemokine receptor-2 expression was also down-regulated at 1 day and 3 days after transplantation.
Conclusions:
Perioperative treatment of simvastatin could suppress the isograft ischemia-reperfusion injury through retarding intragraft monocyte chemoattractant protein-1 accumulation and CC chemokine receptor-2 expression.
