scholarly journals Hepatic cell mobilization for protection against ischemic myocardial injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shu Q. Liu ◽  
John B. Troy ◽  
Chi-Hao Luan ◽  
Roger J. Guillory
Keyword(s):  
Ischemia Reperfusion ◽  
Hepatic Cell ◽  
Ischemic Myocardium ◽  
Cell Nuclei ◽  
Protective Mechanisms ◽  
Specific Expression ◽  
Time Points ◽  
Hepatic Cells ◽  
Cell Mobilization ◽  
Myocardial Ischemia Reperfusion

AbstractThe heart is capable of activating protective mechanisms in response to ischemic injury to support myocardial survival and performance. These mechanisms have been recognized primarily in the ischemic heart, involving paracrine signaling processes. Here, we report a distant cardioprotective mechanism involving hepatic cell mobilization to the ischemic myocardium in response to experimental myocardial ischemia–reperfusion (MI-R) injury. A parabiotic mouse model was generated by surgical skin-union of two mice and used to induce bilateral MI-R injury with unilateral hepatectomy, establishing concurrent gain- and loss-of-hepatic cell mobilization conditions. Hepatic cells, identified based on the cell-specific expression of enhanced YFP, were found in the ischemic myocardium of parabiotic mice with intact liver (0.2 ± 0.1%, 1.1 ± 0.3%, 2.7 ± 0.6, and 0.7 ± 0.4% at 1, 3, 5, and 10 days, respectively, in reference to the total cell nuclei), but not significantly in the ischemic myocardium of parabiotic mice with hepatectomy (0 ± 0%, 0.1 ± 0.1%, 0.3 ± 0.2%, and 0.08 ± 0.08% at the same time points). The mobilized hepatic cells were able to express and release trefoil factor 3 (TFF3), a protein mitigating MI-R injury as demonstrated in TFF3−/− mice (myocardium infarcts 17.6 ± 2.3%, 20.7 ± 2.6%, and 15.3 ± 3.8% at 1, 5, and 10 days, respectively) in reference to wildtype mice (11.7 ± 1.9%, 13.8 ± 2.3%, and 11.0 ± 1.8% at the same time points). These observations suggest that MI-R injury can induce hepatic cell mobilization to support myocardial survival by releasing TFF3.

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

Blood ◽  
2012 ◽  
Vol 120 (26) ◽  
pp. 5217-5223 ◽  
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.

Heart and Mitochondria: Pathophysiology and Implications for Cardiac Surgeons

2017 ◽  
Vol 66 (01) ◽  
pp. 011-019 ◽  
Author(s):  
Michael Schwarzer ◽  
Susanne Rohrbach ◽  
Bernd Niemann
Keyword(s):  
Cardiac Surgery ◽  
Ischemia Reperfusion ◽  
Systemic Circulation ◽  
Cardiac Damage ◽  
Protective Mechanisms ◽  
Ischemic Conditioning ◽  
Disease States ◽  
Similar Disease ◽  
Myocardial Ischemia Reperfusion ◽  
Cardiac Surgeons

Excluding the heart from systemic circulation during cardiac surgery renders the myocardium ischemic, resulting in cardiac damage. In addition, another hit to the myocardium will occur upon restoration of blood flow, in the reperfusion phase. Experimental data from animal models have revealed that loss of cardiac metabolic flexibility and mitochondrial dysfunctions contributes to contractile impairment in hypertrophied, failing, obese, and diabetic hearts. Such diseased hearts are prone to myocardial ischemia–reperfusion (I/R) injury. Although analyses in human cardiac samples are not as comprehensive as animal data, similar disease-associated metabolic and mitochondrial changes exist. Considering increasing age and comorbidities in patients nowadays, it is not surprising that I/R injuries remain a major cause of morbidity and mortality after cardiac surgery. Mitochondria have emerged as critical targets but also key regulators of myocardial I/R injury, and the extent of mitochondrial damage is a major determinant of myocardial I/R injury. Although cardioprotective mechanisms are diverse, many come together and involve steps at the point of mitochondria. We will, therefore, provide a description of mitochondrial alterations observed in various cardiac disease states and discuss the current experimental knowledge of the role of mitochondria in I/R and of potential protective mechanisms against myocardial I/R injury involving mitochondria. Within this review, we will focus on the protection against I/R injury conferred by caloric restriction (CR) and by ischemic conditioning. Further research is needed to establish whether strategies targeting mitochondria, which have been proposed from preclinical studies, could be translated into cardioprotective therapies against I/R injury in patients.

scholarly journals Polypeptide Globular Adiponectin Ameliorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Necroptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Kaiyi Zhu ◽  
Jia Guo ◽  
Xiaoxue Yu ◽  
Que Wang ◽  
Chao Yan ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Endocrine System ◽  
Neonatal Rat ◽  
Protective Mechanisms ◽  
Lactate Dehydrogenase Release ◽  
P38mapk Signaling ◽  
Globular Adiponectin ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

Adiponectin is a small peptide secreted and a key component of the endocrine system and immune system. Although globular adiponectin protects myocardial ischemia/reperfusion-induced cardiomyocyte injury, the protective mechanisms remain largely unresolved. Using a neonatal rat ventricular myocyte hypoxia/reoxygenation model, we investigated the role of its potential mechanisms of necroptosis in globular adiponectin-mediated protection in hypoxia/reoxygenation-induced cardiomyocyte injury as compared to apoptosis. We found that globular adiponectin treatment attenuated cardiomyocyte injury as indicated by increased cell viability and reduced lactate dehydrogenase release following hypoxia/reoxygenation. Immunofluorescence staining and Western blotting demonstrated that both necroptosis and apoptosis were triggered by hypoxia/reoxygenation and diminished by globular adiponectin. Necrostatin-1 (RIP1-specific inhibitor) and Z-VAD-FMK (pan-caspase inhibitor) only mimicked the inhibition of necroptosis and apoptosis, respectively, by globular adiponectin in hypoxia/reoxygenation-treated cardiomyocytes. Globular adiponectin attenuated reactive oxygen species production, oxidative damage, and p38MAPK and NF-κB signaling, all important for necroptosis and apoptosis. Collectively, our study suggests that globular adiponectin inhibits hypoxia/reoxygenation-induced necroptosis and apoptosis in cardiomyocytes probably by reducing oxidative stress and interrupting p38MAPK signaling.

scholarly journals Effectiveness ofPanax ginsengon Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Luo Pei ◽  
Hou Shaozhen ◽  
Dong Gengting ◽  
Chen Tingbo ◽  
Liu Liang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Panax Ginseng ◽  
Testosterone Level ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Ligation ◽  
Protective Mechanisms ◽  
Artery Ligation ◽  
Measured Time ◽  
Myocardial Ischemia Reperfusion

Mechanisms forPanax ginseng’s cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardizedPanax ginsengextract (RSE) was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE’s effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability ofPanax ginsengto protect the heart from myocardial I/R injury.

scholarly journals Disruption of group IVA cytosolic phospholipase A2 attenuates myocardial ischemia-reperfusion injury partly through inhibition of TNF-α-mediated pathway

2012 ◽  
Vol 302 (10) ◽  
pp. H2018-H2030 ◽  
Author(s):  
Yukio Saito ◽  
Kazuhiro Watanabe ◽  
Daisuke Fujioka ◽  
Takamitsu Nakamura ◽  
Jun-ei Obata ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion ◽  
Ischemic Myocardium ◽  
Lv Function ◽  
Myocardial Infarct Size ◽  
Cytosolic Phospholipase ◽  
Tnf Α ◽  
Group Iva ◽  
Myocardial Ischemia Reperfusion

Group IVA cytosolic phospholipase A2 (cPLA2α), which preferentially cleaves arachidonic acid from phospholipids, plays a role in apoptosis and tissue injury. Downstream signals in response to tumor necrosis factor (TNF)-α, a mediator of myocardial ischemia-reperfusion (I/R) injury, involve cPLA2α activation. This study examined the potential role of cPLA2α and its mechanistic link with TNF-α in myocardial I/R injury using cPLA2α knockout (cPLA2α−/−) mice. Myocardial I/R was created with 10-wk-old male mice by 1 h ligation of the left anterior descending coronary artery, followed by 24 h of reperfusion. As a result, compared with wild-type (cPLA2α+/+) mice, cPLA2α−/− mice had a 47% decrease in myocardial infarct size, preservation of echocardiographic left ventricle (LV) function (%fractional shortening: 14 vs. 21%, respectively), and lower content of leukotriene B4 and thromboxane B2 (62 and 50% lower, respectively) in the ischemic myocardium after I/R. Treatment with the TNF-α inhibitor (soluble TNF receptor II/IgG1 Fc fusion protein, sTNFR:Fc) decreased myocardial I/R injury and LV dysfunction in cPLA2α+/+ mice but not cPLA2α−/− mice. sTNFR:Fc also suppressed cPLA2α phosphorylation in the ischemic myocardium after I/R of cPLA2α+/+ mice. Similarly, sTNFR:Fc exerted protective effects against hypoxia-reoxygenation (H/R)-induced injury in the cultured cardiomyocytes from cPLA2α+/+ mice but not cPLA2α−/− cardiomyocytes. H/R and TNF-α induced cPLA2α phosphorylation in cPLA2α+/+ cardiomyocytes, which was reversible by sTNFR:Fc. In cPLA2α−/− cardiomyocytes, TNF-α induced apoptosis and release of arachidonic acid to a lesser extent than in cPLA2α+/+ cardiomyocytes. In conclusion, disruption of cPLA2α attenuates myocardial I/R injury partly through inhibition of TNF-α-mediated pathways.

scholarly journals STVNa Attenuates Isoproterenol-Induced Cardiac Hypertrophy Response through the HDAC4 and Prdx2/ROS/Trx1 Pathways

2020 ◽  
Vol 21 (2) ◽  
pp. 682 ◽  
Author(s):  
Fei Liu ◽  
Hao Su ◽  
Bo Liu ◽  
Ying Mei ◽  
Qingjin Ke ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cell ◽  
Protective Mechanisms ◽  
Histone Deacetylase 4 ◽  
Thioredoxin 1 ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Related Proteins

Recent data show that cardiac hypertrophy contributes substantially to the overall heart failure burden. Mitochondrial dysfunction is a common feature of cardiac hypertrophy. Recent studies have reported that isosteviol inhibits myocardial ischemia-reperfusion injury in guinea pigs and H9c2 cells. This work investigated the protective mechanisms of isosteviol sodium (STVNa) against isoproterenol (Iso)-induced cardiac hypertrophy. We found that STVNa significantly inhibited H9c2 cell and rat primary cardiomyocyte cell surface, restored mitochondrial membrane potential (MMP) and morphological integrity, and decreased the expression of mitochondrial function-related proteins Fis1 and Drp1. Furthermore, STVNa decreased reactive oxygen species (ROS) levels and upregulated the expression of antioxidant factors, Thioredoxin 1 (Trx1) and Peroxiredoxin 2 (Prdx2). Moreover, STVNa restored the activity of histone deacetylase 4 (HDAC4) in the nucleus. Together, our data show that STVNa confers protection against Iso-induced myocardial hypertrophy primarily through the Prdx2/ROS/Trx1 signaling pathway. Thus, STVNA is a potentially effective treatment for cardiac hypertrophy in humans.

Recent Advance on Drug Therapy Related to Myocardial Ischemia Reperfusion Injury

2022 ◽  
Vol 12 (2) ◽  
pp. 299-305
Author(s):  
Yuezhu Liu ◽  
Hua Zeng ◽  
Junmei Xu
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pathological Process ◽  
Ischemic Myocardium ◽  
Research Progress ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Artery Obstruction

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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