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Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery
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Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery
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Journal Article
Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery
2021
Overview
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.
Nitric oxide (NO) is an important gaseous signaling molecule with multiple physiological roles in cardiovascular system. Here the authors develop a cardiac patch with NO releasing function that favors heart repair after myocardial infarction.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 59/57
/ 64/86
/ Animals
/ Cardiotonic Agents - metabolism
/ Cardiotonic Agents - pharmacology
/ Drug Implants - pharmacology
/ Drugs
/ Humanities and Social Sciences
/ Ischemia
/ Macrophage Activation - drug effects
/ Male
/ Mice
/ Myocardial Infarction - metabolism
/ Myocardial Infarction - mortality
/ Myocardial Infarction - prevention & control
/ Myocardial Ischemia - metabolism
/ Myocardial Ischemia - prevention & control
/ Myocardial Reperfusion Injury - metabolism
/ Myocardial Reperfusion Injury - prevention & control
/ Nitrates
/ Nitrogen Oxides - metabolism
/ Polymers
/ Rats
/ Science
/ Swine
