Recent Advance on Drug Therapy Related to Myocardial Ischemia Reperfusion Injury

Myocardial ischemia reperfusion injury (MIRI) means complete or partial artery obstruction of coronary artery, and ischemic myocardium will be recirculating in a period of time. Although the ischemic myocardium can be restored to normal perfusion, its tissue damage will instead be progressive. An aggravated pathological process. MIRI is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. Therefore, the research and development of drugs for the prevention and treatment of this period has also become the focus. This article first studied pathophysiology of MIRI, and reviewed the research progress of MIRI-related drugs. Research results show that: MIRI is inevitable for myocardial ischemia, with the possible to double damage via the ischemic condition. Therefore, it is a serious complication and one of the most popular diseases in the world. It has always been difficult to find an effective treatment for this disease, because it is difficult to explore the inflammation behind its pathophysiology.

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Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice

Blood ◽

10.1182/blood-2012-06-439935 ◽

2012 ◽

Vol 120 (26) ◽

pp. 5217-5223 ◽

Cited By ~ 65

Author(s):

Simon F. De Meyer ◽

Alexander S. Savchenko ◽

Michael S. Haas ◽

Daphne Schatzberg ◽

Michael C. Carroll ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ischemic Myocardium ◽

Wild Type ◽

Myocardial Ischemia Reperfusion Injury ◽

Anti Inflammatory ◽

Myocardial Ischemia Reperfusion ◽

Inflammatory Effect

Abstract Coronary heart disease is a major cause of death in the western world. Although essential for successful recovery, reperfusion of ischemic myocardium is inevitably associated with reperfusion injury. To investigate a potential protective role of ADAMTS13, a protease cleaving von Willebrand factor multimers, during myocardial ischemia/reperfusion, we used a mouse model of acute myocardial infarction. We found that Adamts13−/− mice developed larger myocardial infarctions than wild-type control mice, whereas treatment of wild-type mice with recombinant human ADAMTS13 (rhADAMTS13) led to smaller infarctions. The protective effect of ADAMTS13 was further confirmed by a significant reduction of cardiac troponin-I release and less myocardial apoptosis in mice that received rhADAMTS13 compared with controls. Platelets adherent to the blood vessel wall were observed in few areas in the heart samples from mice treated with vehicle and were not detected in samples from mice treated with rhADAMTS13. However, we observed a 9-fold reduction in number of neutrophils infiltrating ischemic myocardium in mice that were treated with rhADAMTS13, suggesting a potent anti-inflammatory effect of ADAMTS13 during heart injury. Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury.

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Histone deacetylase HDAC4 participates in the pathological process of myocardial ischemia-reperfusion injury via MEKK1/JNK pathway by binding to miR-206

Cell Death Discovery ◽

10.1038/s41420-021-00601-1 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Qingman Li ◽

Lijie Zhu ◽

Fangqing Niu ◽

Qingmin Li ◽

Che Wang ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Pathological Process ◽

Cardiomyocyte Apoptosis ◽

Down Regulation ◽

Jnk Pathway ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

AbstractHistone deacetylases (HDACs) and microRNAs (miRs) have been reported to exert pivotal roles on the pathogenesis of myocardial ischemia-reperfusion injury (MIRI). Therefore, the present study was performed to define the underlying role of HDAC4 and miR-206 in the pathological process of MIRI. An IRI rat model was established. The interaction between HDAC4 and the promoter region of miR-206 was determined using ChIP, and that between miR-206 and mitogen-activated protein kinase kinase kinase 1 (MEKK1) was determined using dual luciferase reporter gene assay. After the loss- or gain-of-function assay in cardiomyocytes, western blot analysis, RT-qPCR, TUNEL, and ELISA assay were performed to define the roles of HDAC4, miR-206, and MEKK1. Up-regulation of HDAC4 and down-regulation of miR-206 occurred in rat myocardial tissues and cardiomyocytes in MIRI. HDAC4 down-regulation or miR-206 up-regulation contributed to reduced cell apoptosis and the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA), while elevating the superoxide dismutase (SOD) and glutathione (GSH) contents. Meanwhile, HDAC4 silencing promoted the expression of miR-206, which targeted and negatively regulated MEKK1. Then inhibition of JNK phosphorylation reduced the cardiomyocyte apoptosis to alleviate MIRI. Coherently, HDAC4 silencing could up-regulate the expression of miR-206 to reduce cardiomyocyte apoptosis and inhibit oxidative stress, and exerting a protective effect on MIRI via the MEKK1/JNK pathway.

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Protective Effect of Tetramethylpyrazine on Myocardial Ischemia-Reperfusion Injury

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/107501 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 32

Author(s):

Weidong Qian ◽

Xingjiang Xiong ◽

Zhuyuan Fang ◽

Haiting Lu ◽

Zhensheng Wang

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Cell Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Research Progress ◽

Protective Effects ◽

Myocardial Cells ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Myocardial ischemia-reperfusion injury (MIRI) is a common pathological and physiological phenomenon. Tetramethylpyrazine is the extract of the traditional Chinese medicine Chuanxiong, which can exert protective effects on MIRI in multiple ways. This paper reviewed the current research progress and evidence about the cardiovascular effects of tetramethylpyrazine, which included protecting mitochondria and improving energy metabolism, scavenging oxygen free radicals (OFRs) to inhibit lipid peroxidation, attenuating calcium (Ca2+) overload and maintaining Ca2+homeostasis in cells, inhibiting apoptosis and protecting myocardial cells, interfering with the inflammatory reaction and mitigating cell injury, interfering with cell signaling pathways, and improving function of endothelial cells and protecting myocardial cells. However, further rigorously designed randomized controlled trials are warranted.

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Tregs Biomimetic Nanoparticle to Reprogram Inflammatory and Redox Microenvironment in Infarct Tissue to Inhibit the Remodeling of the Left Ventricle of Myocardial Ischemia Reperfusion Injury in Mice

10.21203/rs.3.rs-1125947/v1 ◽

2021 ◽

Author(s):

Fangyuan Li ◽

Daozhou Liu ◽

Miao Liu ◽

Qifeng Ji ◽

Bangle Zhang ◽

...

Keyword(s):

Myocardial Ischemia ◽

Left Ventricle ◽

Protein Expression ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ischemic Myocardium ◽

Increased Risk ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Abstract Background At present, patients with myocardial infarction remain an increased risk for myocardial ischemia/reperfusion injury (MI/RI), which currently lacks an effective therapeutic method. It is still a bottleneck that effectively deliver drug to ischemic myocardium to treat MI/RI. Inspired by the protective effect of regulatory T cells (Tregs) on MI/RI and natural role of platelets in adhesion with damaged blood vessel in heart during myocardial infarct, a Tregs biomimetic nanoparticle (CsA@PPTK) was prepared by camouflaging a cyclosporin A (CsA)-loaded and reactive oxygen species (ROS)-sensitive nanoparticle with platelet membrane. Results In MI/RI mice, CsA@PPTK could be preferentially delivered to ischemic myocardium. CsA@PPTK significantly scavenged ROS in ischemic myocardium, while it also markedly increased the generation of Tregs and the ratio of M2 type macrophage to M1 type macrophage in ischemic myocardium. Furthermore, CsA@PPTK significantly attenuated apoptosis of cardiomyocytes in ischemic myocardium. At the same time, CsA@PPTK obviously reduced the infarct size, fibrosis area and the protein expression of MMP-9, while increased the protein expression of CX43. Subsequently, the remodeling of the left ventricle was significant alleviated. Finally, heart function of MI/RI mice was markedly improved. Conclusion CsA@PPTK has great potential in the treatment of MI/RI. This study provides a novel class of heart protective biomimetic platform that is beneficial for treatment of MI/RI.

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