Enhancing miR-19a/b induced cardiomyocyte proliferation in infarcted hearts by alleviating oxidant stress and controlling miR-19 release

通过减轻氧化应激和控制 miR-19 释放来增强 miR-19a/b 诱导的梗死心脏心肌细胞增殖

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作者:Kai Wang, Jun Wen, Tian Liang, Haijun Hu, Shifen Li, Liyin Shen, Tanchen Ren, Yuejun Yao, Jieqi Xie, Jie Ding, Jinghai Chen, Yi-Da Tang, Yang Zhu, Changyou Gao

Abstract

Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.

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