Qiang Su1,2, Lang Li1, Jinmin Zhao3,2, Yuhan Sun1, Huafeng Yang1. 1. Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. 2. Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China. 3. Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Abstract
BACKGROUND/AIMS: The local inflammatory response caused by coronary microembolization (CME) is the primary cause of progressive cardiac dysfunction. The PDCD4/NF-κB/TNF-α signaling pathway plays a significant role in CME-induced myocardial Inflammation. Trimetazidine (TMZ) reduces myocardial injury, caused by percutaneous coronary intervention, through relieving the CME-induced myocardial systolic dysfunction. Therefore, the present study investigated the role of TMZ pre-treatment in the protection of myocardium after CME and PDCD4/NF-κB/TNF-α in mini pigs. METHODS: 20 Bama mini pigs were randomized into sham operation (sham), microembolization (CME), TMZ, and siRNA-PDCD4 groups (n = 5). The CME model was established by injecting polyethylene microspheres via microcatheter into the left anterior descending coronary artery. The TMZ group was injected 2.5 mg/kg drug via ear vein 30 min before CME; whereas, the siRNA-PDCD4 group was transfected with PDCD4 siRNA at the left anterior descending coronary artery via microcatheter 72h before CME. Cardiac function indexes were measured using cardiac echocardiography. The mRNA expression of PDCD4 and TNF-α in the myocardium was detected by quantitative fluorescence PCR, and the protein expression of PDCD4, NF-κB (p65), and TNF-α by Western blot. RESULTS: Echocardiographic parameters showed lower cardiac function and higher serum cTnI level in the CME group than sham, which was manifested as reduced left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS), cardiac output (CO), and increased left ventricular diastolic diameter (LVEDd). Compared to the CME group, the CME-induced cardiac function injury was reduced, and the serum cTnI level was decreased in the TMZ and siRNA-PDCD4 groups. The expressions of PDCD4, NF-κB (p65), and TNF-α were significantly increased in the CME than the sham groups (P < 0.05), and significantly decreased in the TMZ and siRNA-PDCD4 groups than the CME group (P < 0.05). CONCLUSION: TMZ pretreatment effectively reduced the myocardial damage caused by CME via inhibiting the PDCD4/NF-κB/ TNF-α pathway in cardiomyocytes.
BACKGROUND/AIMS: The local inflammatory response caused by coronary microembolization (CME) is the primary cause of progressive cardiac dysfunction. The PDCD4/NF-κB/TNF-α signaling pathway plays a significant role in CME-induced myocardial Inflammation. Trimetazidine (TMZ) reduces myocardial injury, caused by percutaneous coronary intervention, through relieving the CME-induced myocardial systolic dysfunction. Therefore, the present study investigated the role of TMZ pre-treatment in the protection of myocardium after CME and PDCD4/NF-κB/TNF-α in mini pigs. METHODS: 20 Bama mini pigs were randomized into sham operation (sham), microembolization (CME), TMZ, and siRNA-PDCD4 groups (n = 5). The CME model was established by injecting polyethylene microspheres via microcatheter into the left anterior descending coronary artery. The TMZ group was injected 2.5 mg/kg drug via ear vein 30 min before CME; whereas, the siRNA-PDCD4 group was transfected with PDCD4 siRNA at the left anterior descending coronary artery via microcatheter 72h before CME. Cardiac function indexes were measured using cardiac echocardiography. The mRNA expression of PDCD4 and TNF-α in the myocardium was detected by quantitative fluorescence PCR, and the protein expression of PDCD4, NF-κB (p65), and TNF-α by Western blot. RESULTS: Echocardiographic parameters showed lower cardiac function and higher serum cTnI level in the CME group than sham, which was manifested as reduced left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS), cardiac output (CO), and increased left ventricular diastolic diameter (LVEDd). Compared to the CME group, the CME-induced cardiac function injury was reduced, and the serum cTnI level was decreased in the TMZ and siRNA-PDCD4 groups. The expressions of PDCD4, NF-κB (p65), and TNF-α were significantly increased in the CME than the sham groups (P < 0.05), and significantly decreased in the TMZ and siRNA-PDCD4 groups than the CME group (P < 0.05). CONCLUSION:TMZ pretreatment effectively reduced the myocardial damage caused by CME via inhibiting the PDCD4/NF-κB/ TNF-α pathway in cardiomyocytes.
Authors: Tao Li; Yu Ma; Min Wang; Tao Wang; Jing Wei; Rui Ren; Min He; Guixue Wang; Johnson Boey; David G Armstrong; Wuquan Deng; Bing Chen Journal: Infect Drug Resist Date: 2019-01-29 Impact factor: 4.003
Authors: Lucia Gatta; Laura Vitiello; Stefania Gorini; Sergio Chiandotto; Paola Costelli; Anna Maria Giammarioli; Walter Malorni; Giuseppe Rosano; Elisabetta Ferraro Journal: Oncotarget Date: 2017-12-08