Effects of atorvastatin on PDCD4/NF-κB/TNF-α signaling pathway during coronary microembolization of miniature pigs.
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.
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Qiang
Q
Su
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. Electronic address: drlilang@163.com.
Lang
L
Li
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Tao
T
Liu
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Jiangyou
J
Wang
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
You
Y
Zhou
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Yangchun
Y
Liu
D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004617:Embolism / Q000209:etiology*; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine; D013556:Swine, Miniature; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin
Atorvastatin; Cardiac function; Coronary microembolization; Programmed cell death 4