Cardiac cell proliferation is not necessary for exercise-induced cardiac growth but required for its protection against ischaemia/reperfusion injury.
Cardiac cell proliferation is not necessary for exercise-induced cardiac growth but required for its protection against ischaemia/reperfusion injury.
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心肌细胞增殖对于运动诱导的心脏生长不是必需的，但对于防止缺血/再灌注损伤是必需的
DOI：
10.1111/jcmm.13078
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发表时间：
2017-08
影响因子：
5.3
通讯作者：
Xiao J
中科院分区：
文献类型：
--
作者：
Bei Y;Fu S;Chen X;Chen M;Zhou Q;Yu P;Yao J;Wang H;Che L;Xu J;Xiao J
成年人的心脏保留有限的再生能力以应对损伤。虽然运动可以减少心脏缺血/再灌注（I/R）损伤，但心肌细胞增殖（包括新形成的心肌细胞）的相对贡献仍不清楚。使用4周游泳小鼠模型诱导心脏生理生长。同时，通过腹膜内注射给予小鼠在细胞周期的S期起作用的抑制剂5-氟尿嘧啶（5-FU）。使用EdU和Ki-67免疫标记，我们发现运动诱导的心肌细胞增殖被5-FU钝化。此外，运动后心脏大小和重量的增长没有改变，这可能是由于运动诱导的心肌细胞肥大不受5-FU的影响，如麦胚凝集素染色所示。同时，运动或5-FU均未改变病理性肥大的标志物（包括ANP和BNP），表明在5-FU存在下仍存在生理性生长。此外，我们发现，心肌细胞增殖的关键调节因子CITED 4被5-FU阻断。同时，C/EBPβ（一种负责细胞增殖和肥大的转录因子）未被5-FU处理改变。重要的是，当用5-FU处理的小鼠的心脏细胞增殖减弱时，运动在减少心脏I/R损伤方面的作用可以被消除。总之，心肌细胞增殖不是运动诱导的心脏生理生长所必需的，但它是运动相关的I/R损伤保护所必需的。
The adult heart retains a limited ability to regenerate in response to injury. Although exercise can reduce cardiac ischaemia/reperfusion (I/R) injury, the relative contribution of cardiac cell proliferation including newly formed cardiomyocytes remains unclear. A 4‐week swimming murine model was utilized to induce cardiac physiological growth. Simultaneously, the antineoplastic agent 5‐fluorouracil (5‐FU), which acts during the S phase of the cell cycle, was given to mice via intraperitoneal injections. Using EdU and Ki‐67 immunolabelling, we showed that exercise‐induced cardiac cell proliferation was blunted by 5‐FU. In addition, the growth of heart in size and weight upon exercise was unaltered, probably due to the fact that exercise‐induced cardiomyocyte hypertrophy was not influenced by 5‐FU as demonstrated by wheat germ agglutinin staining. Meanwhile, the markers for pathological hypertrophy, including ANP and BNP, were not changed by either exercise or 5‐FU, indicating that physiological growth still developed in the presence of 5‐FU. Furthermore, we showed that CITED4, a key regulator for cardiomyocyte proliferation, was blocked by 5‐FU. Meanwhile, C/EBPβ, a transcription factor responsible for both cellular proliferation and hypertrophy, was not altered by treatment with 5‐FU. Importantly, the effects of exercise in reducing cardiac I/R injury could be abolished when cardiac cell proliferation was attenuated in mice treated with 5‐FU. In conclusion, cardiac cell proliferation is not necessary for exercise‐induced cardiac physiological growth, but it is required for exercise‐associated protection against I/R injury.
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影响因子：
20.1
作者：
Calvert JW;Condit ME;Aragón JP;Nicholson CK;Moody BF;Hood RL;Sindler AL;Gundewar S;Seals DR;Barouch LA;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
--
作者：
Tao L;Bei Y;Zhang H;Xiao J;Li X
通讯作者：
Li X
影响因子：
37.8
作者：
Santos-Gallego, Carlos G.;Vahl, Torsten P.;Badimon, Juan J.
通讯作者：
Badimon, Juan J.
影响因子：
64.5
作者：
Ellison, Georgina M.;Vicinanza, Carla;Nadal-Ginard, Bernardo
通讯作者：
Nadal-Ginard, Bernardo
Notch 激活静止心肌细胞的细胞周期重入和进展。
DOI：
10.1083/jcb.200806104
发表时间：
2008-10-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Campa VM;Gutiérrez-Lanza R;Cerignoli F;Díaz-Trelles R;Nelson B;Tsuji T;Barcova M;Jiang W;Mercola M
通讯作者：
Mercola M