Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery.
Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery.
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硝酸盐功能化贴片通过局部一氧化氮输送提供心脏保护并改善心肌梗塞后的心脏修复
DOI：
10.1038/s41467-021-24804-3
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发表时间：
2021-07-23
影响因子：
16.6
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
Zhu D;Hou J;Qian M;Jin D;Hao T;Pan Y;Wang H;Wu S;Liu S;Wang F;Wu L;Zhong Y;Yang Z;Che Y;Shen J;Kong D;Yin M;Zhao Q
一氧化氮（NO）是一种短寿命的信号分子，在心血管系统中起着关键作用。有机硝酸盐代表了一类用于治疗冠状动脉疾病的NO供体药物，其通过经常导致不良反应的全身血管系统的血管舒张起作用。在此，我们设计了一种硝酸盐功能化贴片，其中硝酸盐药理学官能团共价结合到可生物降解的聚合物上，从而将小分子药物转化为治疗性生物材料。当植入到心肌上时，贴片通过逐步生物转化局部释放NO，并且由于缺血微环境，NO生成在梗死心肌中显著增强，这产生了靶向心脏保护以及增强的心脏修复。在临床相关的猪心肌梗死模型中进一步证实了治疗功效。所有这些结果支持了这种功能性贴片通过不同于常规有机硝酸盐药物的治疗机制治疗缺血性心脏病的转化潜力。
Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.
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脱细胞斑马鱼心脏外基质会诱导哺乳动物心脏再生。
影响因子：
13.6
作者：
Chen WC;Wang Z;Missinato MA;Park DW;Long DW;Liu HJ;Zeng X;Yates NA;Kim K;Wang Y
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DOI：
10.1124/jpet.113.203356
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影响因子：
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影响因子：
24
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Loscalzo J
DOI：
10.1016/s0735-1097(01)01414-0
发表时间：
2001-09-01
影响因子：
24
作者：
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通讯作者：
Parker, JD