Identification of potential molecular mechanisms and small molecule drugs in myocardial ischemia/reperfusion injury

Emerging evidence has demonstrated that regulatory noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs) and miRNAs, play crucial roles in the initiation and progress of myocardial ischemia-reperfusion injury (MIRI), which is associated with autophagy, apoptosis and necrosis of cardiomyocytes, as well as oxidative stress, inflammation and mitochondrial dysfunction. LncRNAs serve as a precursor or host of miRNAs and directly/indirectly affecting miRNAs via competitive binding or sponge effects. Simultaneously, miRNAs post-transcriptionally regulate the expression of genes by targeting various mRNA sequences due to their imperfect pairing with mRNAs. This review summarizes the potential regulatory role of lncRNA–miRNA–mRNA axes in MIRI and related molecular mechanisms of cardiac disorders, also provides insight into the potential therapies for MIRI-induced diseases.

Download Full-text

Iminostilbene, a novel small-molecule modulator of PKM2, suppresses macrophage inflammation in myocardial ischemia–reperfusion injury

Journal of Advanced Research ◽

10.1016/j.jare.2020.09.001 ◽

2020 ◽

Author(s):

Shan Lu ◽

Yu Tian ◽

Yun Luo ◽

Xudong Xu ◽

Wenxiu Ge ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Small Molecule ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Ischemia Reperfusion Injury ◽

Small Molecule Modulator ◽

Myocardial Ischemia Reperfusion

Download Full-text

The Emerging Role of Thioredoxin-Interacting Protein in Myocardial Ischemia/Reperfusion Injury

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248416675731 ◽

2016 ◽

Vol 22 (3) ◽

pp. 219-229 ◽

Cited By ~ 12

Author(s):

Bing F. Wang ◽

Jun Yoshioka

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Interacting Protein ◽

Glucose Transporter 1 ◽

Thioredoxin Interacting Protein ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Myocardial ischemia/reperfusion injury represents a major threat to human health and contributes to adverse cardiovascular outcomes worldwide. Despite the identification of numerous molecular mechanisms, understanding of the complex pathophysiology of this clinical syndrome remains incomplete. Thioredoxin-interacting protein (Txnip) has been of great interest in the past decade since it has been reported to be a critical regulator in human diseases with several important cellular functions. Thioredoxin-interacting protein binds to and inhibits thioredoxin, a redox protein that neutralizes reactive oxygen species (ROS), and through its interaction with thioredoxin, Txnip sensitizes cardiomyocytes to ROS-induced apoptosis. Interestingly, evidence from recent studies also suggests that some of the effects of Txnip may be unrelated to changes in thioredoxin activity. These pleiotropic effects of Txnip are mediated by interactions with other signaling molecules, such as nod-like receptor pyrin domain-containing 3 inflammasome and glucose transporter 1. Indeed, Txnip has been implicated in the regulation of inflammatory response and glucose homeostasis during myocardial ischemia/reperfusion injury. This review attempts to make the case that in addition to interacting with thioredoxin, Txnip contributes to some of the pathological consequences of myocardial ischemia and infarction through endogenous signals in multiple molecular mechanisms.

Download Full-text