Open AccessAn Injectable Dual‐Function Hydrogel Protects Against Myocardial Ischemia/Reperfusion Injury by Modulating ROS/NO Disequilibrium
Author(s) -
Hao Tian,
Qian Meng,
Zhang Yating,
Liu Qi,
Midgley Adam C.,
Liu Yangping,
Che Yongzhe,
Hou Jingli,
Zhao Qiang
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202105408
Subject(s) - reactive oxygen species , pharmacology , reperfusion injury , oxidative stress , nitric oxide , ischemia , inflammation , cardiac function curve , medicine , chemistry , cardiology , heart failure , immunology , biochemistry
Acute myocardial infarction (MI) is the leading cause of death worldwide. Exogenous delivery of nitric oxide (NO) to the infarcted myocardium has proven to be an effective strategy for treating MI due to the multiple physiological functions of NO. However, reperfusion of blood flow to the ischemic tissues is accompanied by the overproduction of toxic reactive oxygen species (ROS), which can further exacerbate tissue damage and compromise the therapeutic efficacy. Here, an injectable hydrogel is synthesized from the chitosan modified by boronate‐protected diazeniumdiolate (CS‐B‐NO) that can release NO in response to ROS stimulation and thereby modulate ROS/NO disequilibrium after ischemia/reperfusion (I/R) injury. Furthermore, administration of CS‐B‐NO efficiently attenuated cardiac damage and adverse cardiac remodeling, promoted repair of the heart, and ameliorated cardiac function, unlike a hydrogel that only released NO, in a mouse model of myocardial I/R injury. Mechanistically, regulation of the ROS/NO balance activated the antioxidant defense system and protected against oxidative stress induced by I/R injury via adaptive regulation of the Nrf2‐Keap1 pathway. Inflammation is then reduced by inhibition of the activation of NF‐ κ B signaling. Collectively, these results show that this dual‐function hydrogel may be a promising candidate for the protection of tissues and organs after I/R injury.