title: Mechanism of programmed cell death factor 4/nuclear factor-κB signaling pathway in porcine coronary micro-embolization-induced cardiac dysfunction.
abstract: The aim of this study was to investigate the role of the programmed cell death factor 4 (PDCD4)/nuclear factor-κB (NF-κB) signaling pathway in coronary micro-embolism (CME)-induced inflammatory responses and cardiac dysfunction in a porcine model. Bama miniature pigs were randomly divided into four groups (n = 5 per group). Micro-embolization balls or saline were infused through a microcatheter in the left anterior descending (LAD) artery in the CME and Sham groups, respectively. PDCD4 siRNA or control siRNA mixed with transfection reagent was infused via the LAD artery 72 h before CME induction in the CME + siRNA-PDCD4 and siRNA-control groups, respectively. Cardiac function was evaluated with ultrasound. Tissue biopsy was stained with hematoxylin-eosin (HE) and hematoxylin basic fuchsin picric acid (HBFP) to measure infarction area. Myocardial PDCD4 and tumor necrosis factor-α (TNF-α) mRNA and protein expression were analyzed by quantitative PCR and Western blotting. NF-κB activity was evaluated in gel electrophoretic mobility shift assay. Echocardiographic parameters showed that compared with the sham group, the CME group had impaired heart function, manifested as systolic dysfunction and left ventricular dilatation (reduced left ventricular ejection fraction [LVEF], left ventricular fractional shortening [FS], and cardiac output [CO] [P < 0.05] and increased left ventricular end-diastolic diameter [LVEDd] [P < 0.05]). Compared with the CME group, the CME + siRNA-PDCD4 group had attenuated CME-induced cardiac function damage (increased LVEF, FS and CO [P < 0.05] and reduced LVEDd [P < 0.05]). Compared with the sham group, the CME group had significantly increased PDCD4 and TNF-α mRNA and protein expression and increased NF-κB activity (P < 0.05). These effects were significantly inhibited in the CME + siRNA-PDCD4 group (P < 0.05). In conclusion, PDCD4/NF-κB signaling pathway activation is an important mechanism for CME-induced cardiac dysfunction, suggesting that inhibition of PDCD4/NF-κB signaling pathway may be a potential target for the prevention and treatment of CME.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China drlilang@163.com.
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Jiangyou
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001706:Biopsy; D002302:Cardiac Output; D003331:Coronary Vessels / Q000473:pathology*; D004195:Disease Models, Animal; D004617:Embolism / Q000473:pathology; D005260:Female; D007249:Inflammation; D008297:Male; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010851:Picrates / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D013556:Swine, Miniature; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*; D016277:Ventricular Function, Left
chemical_list: D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D010851:Picrates; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; C005858:picric acid
keywords: Coronary micro-embolization; cardiac function; nuclear factor-κB; programmed cell death factor 4; vascular intervention