Cardiac resident macrophages are involved in hypoxia‑induced postnatal cardiomyocyte proliferation.
Cardiac resident macrophages are involved in hypoxia‑induced postnatal cardiomyocyte proliferation.
复制标题
心脏常驻巨噬细胞参与缺氧诱导的出生后心肌细胞增殖
DOI：
10.3892/mmr.2017.6432
复制
发表时间：
2017-06
影响因子：
3.4
通讯作者：
Xiao YB
中科院分区：
文献类型：
--
作者：
Liu B;Zhang HG;Zhu Y;Jiang YH;Luo GP;Tang FQ;Jian Z;Xiao YB
诱导心肌细胞增殖是逆转心肌损耗最有希望的方法，作为心血管疾病的治疗方法越来越重要。缺氧和巨噬细胞以前被独立报道促进小鼠心肌细胞增殖。然而，缺氧是否促进人类心肌细胞增殖，以及心肌细胞增殖中缺氧和巨噬细胞之间的关联，据我们所知，以前还没有研究过。本研究观察了22例非紫绀型和29例紫绀型患者的心肌细胞增殖情况。随后在缺氧小鼠模型（15%O2）中进行心肌细胞增殖，并分析巨噬细胞亚群。使用C-C趋化因子受体2型（CCR 2）抑制剂增加驻留巨噬细胞的数量，以研究巨噬细胞对心肌细胞增殖的影响。结果表明，紫绀婴儿组的心肌细胞增殖显着增加相比，非紫绀婴儿组和缺氧处理的C57 BL/6 J新生儿证实了缺氧诱导的心肌细胞增殖。然而，缺氧并没有诱导分离的心肌细胞增殖。值得注意的是，缺氧处理增加了新生儿心脏中心脏驻留巨噬细胞的数量。此外，增加驻留巨噬细胞的数量显着增强心肌细胞增殖。总之，出生后缺氧促进了人类和动物心肌细胞的增殖，心脏驻留巨噬细胞可能参与了这一过程。因此，这种新的机制可能为心血管疾病的治疗提供一种有前途的策略。
Induction of cardiomyocyte proliferation, the most promising approach to reverse myocardial attrition, has been gaining importance as a therapy for cardiovascular disease. Hypoxia and macrophages were previously independently reported to promote cardiomyocyte proliferation in mice. However, whether hypoxia promotes cardiomyocyte proliferation in humans, and the association between hypoxia and macrophages in cardiomyocyte proliferation, have not to the best of our knowledge been previously investigated. The present study investigated the cardiomyocyte proliferation in 22 acyanotic and 29 cyanotic patients. Cardiomyocyte proliferation in a hypoxic mouse model (15% O2) was subsequently performed and the macrophage subsets were analyzed. A C-C chemokine receptor type 2 (CCR2) inhibitor was used to increase the number of resident macrophages in order to investigate the effect of macrophages on cardiomyocyte proliferation. The results demonstrated that cardiomyocyte proliferation in the cyanotic infant group was significantly increased compared with the acyanotic infant group and the hypoxia-treated C57BL/6J neonates confirmed the hypoxia-induced cardiomyocyte proliferation. However, hypoxia did not induce the proliferation of isolated cardiomyocytes. Notably, hypoxia treatment increased the number of cardiac resident macrophages in neonate hearts. Furthermore, increasing the number of resident macrophages significantly enhanced cardiomyocyte proliferation. In conclusion, postnatal hypoxia promoted cardiomyocyte proliferation in humans and animals, and cardiac resident macrophages may be involved in this process. Therefore, this novel mechanism may provide a promising strategy for cardiovascular disease treatment.