Effect of atorvastatin (Lipitor) on myocardial apoptosis and caspase-8 activation following coronary microembolization |
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Authors: | Li Lang Su Qiang Wang Yan Dai Rixin Lu Yongguang Su Bo Zhao Yongxiang |
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Institution: | (1) Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China |
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Abstract: | We determined the effect of atorvastatin on myocardial apoptosis and caspase-8 activation following coronary microembolization
(CME) in a rat model. For this, 50 rats were randomly and equally divided into CME; sham-operated (control); atorvastatin
lavage; gastric lavage control; and caspase-8 inhibitor (CHO) groups. In CME animals, a microembolization ball was injected
through the left ventricle. Sham animals were injected with normal saline (NS). Atorvastatin group received atorvastatin gastric
lavage once-a-day, 1 week before surgery. Gastric lavage controls had similar lavage with NS. CHO group was i.p-injected (CHO:
10 mg/kg) 30 min before surgery. Cardiac indices in each group were determined by echocardiography 6-h postoperatively. TUNEL
assay and western blot were used for myocardial apoptosis and expression of caspases-3/-8, respectively. Echocardiography
data show that left ventricular ejection fraction (LVEF) in CME group was significantly decreased (P < 0.05) compared with sham controls. Besides, left ventricular fractional shortening (FS) and cardiac output (CO) were also
decreased with an increase in left ventricular end-diastolic dimension (LVEDd). Atorvastatin and CHO animals had significantly
improved (P < 0.05) cardiac function compared with CME group. Myocardial apoptosis and activation levels of caspases-3/-8 were significantly
increased (P < 0.05) compared with sham; myocardial apoptosis and activation levels of caspases-3/-8 were significantly decreased (P < 0.05) in atorvastatin and CHO groups compared with CME group. In conclusion, atorvastatin pretreatment suppressed post-CME
myocardial apoptosis and improved cardiac function through the blockade of a myocardial death receptor-mediated apoptotic
pathway. |
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