TNF-α-induced cardiomyocyte apoptosis contributes to cardiac dysfunction after coronary microembolization in mini-pigs.
TNF-α-induced cardiomyocyte apoptosis contributes to cardiac dysfunction after coronary microembolization in mini-pigs.
复制标题
TNF-α诱导的心肌细胞凋亡导致小型猪冠状动脉微栓塞后心功能不全
DOI:
10.1111/jcmm.12342
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发表时间:
2014-10
影响因子:
5.3
通讯作者:
Ge JB
中科院分区:
文献类型:
--
作者:
Chen ZW;Qian JY;Ma JY;Chang SF;Yun H;Jin H;Sun AJ;Zou YZ;Ge JB
This experimental study was designed to clarify the relationship between cardiomyocyte apoptosis and tumour necrosis factor-alpha (TNF-α) expression, and confirm the effect of TNF-α on cardiac dysfunction after coronary microembolization (CME) in mini-pigs. Nineteen mini-pigs were divided into three groups: sham-operation group (n = 5), CME group (n = 7) and adalimumab pre-treatment group (n = 7; TNF-α antibody, 2 mg/kg intracoronary injection before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th hour and 1 week after procedure. Cardiomyocyte apoptosis was detected by cardiac-TUNEL staining, and caspase-3 and caspase-8 were detected by RT-PCR and immunohistochemistry. Furthermore, serum TNF-α, IL-6 and troponin T were analysed, while myocardial expressions of TNF-α and IL-6 were detected. Both TNF-α expression (serum level and myocardial expression) and average number of apoptotic cardiomyocyte nuclei were significantly increased in CME group compared with the sham-operation group. Six hours after CME, left ventricular end-systolic volume (LVESV) was increased and the left ventricular ejection fraction (LVEF) was decreased in CME group. Pre-treatment with adalimumab not only significantly improved LVEF after CME (6th hour: 54.9 ± 2.3% versus 50.4 ± 3.9%, P = 0.036; 1 week: 56.7 ± 4.2% versus 52.7 ± 2.9%, P = 0.041), but also suppressed cardiomyocyte apoptosis and the expression of caspase-3 and caspase-8. Meanwhile, the average number of apoptotic cardiomyocytes nuclei was inversely correlated with LVEF (r = −0.535, P = 0.022). TNF-α-induced cardiomyocyte apoptosis is likely involved in cardiac dysfunction after CME. TNF-α antibody therapy suppresses cardiomyocyte apoptosis and improves early cardiac function after CME.
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影响因子:
37.8
作者:
Skyschally, A;Haude, M;Heusch, G
通讯作者:
Heusch, G
影响因子:
39.3
作者:
Canton, M;Skyschally, A;Heusch, G
通讯作者:
Heusch, G
影响因子:
14
作者:
Breuckmann, Frank;Nassenstein, Kai;Barkhausen, Joerg
通讯作者:
Barkhausen, Joerg
影响因子:
2.6
作者:
Li, Lang;Su, Qiang;Zhao, Yongxiang
通讯作者:
Zhao, Yongxiang
影响因子:
20.1
作者:
Kleinbongard, Petra;Boese, Dirk;Heusch, Gerd
通讯作者:
Heusch, Gerd