The potentials of distinct functions of autophagy to be targeted for attenuation of myocardial ischemia/reperfusion injury in preclinical studies: an up-to-date review

Mokhtari, Behnaz; Badalzadeh, Reza

doi:10.1007/s13105-021-00824-x

Cited by 20 publications

(12 citation statements)

References 96 publications

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“…Studies have shown that the combined effect of IPostC and alpha-lipoic acid in diabetic rats’ hearts can reduce the infarct size of isolated diabetic hearts by restoring autophagic flux and mitochondrial function. The experimental results coincide with the common expectation that induction of controlled autophagy at the appropriate time and level and inhibition of inappropriate autophagy can exert cardioprotective effects ( 90 ). However, the experiment did not give the specific protective mechanism of the cardioprotective strategy alone.…”

Section: Multi-target Strategies For Myocardial Ischemia-reperfusion ...supporting

confidence: 85%

Preclinical multi-target strategies for myocardial ischemia-reperfusion injury

Gao

2022

Front. Cardiovasc. Med.

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Despite promising breakthroughs in diagnosing and treating acute coronary syndromes, cardiovascular disease’s high global mortality rate remains indisputable. Nearly half of these patients died of ischemic heart disease. Primary percutaneous coronary intervention (PCI) and coronary artery bypass grafting can rapidly restore interrupted blood flow and become the most effective method for salvaging viable myocardium. However, restoring blood flow could increase the risk of other complications and myocardial cell death attributed to myocardial ischemia-reperfusion injury (IRI). How to reduce the damage of blood reperfusion to ischemic myocardium has become an urgent problem to be solved. In preclinical experiments, many treatments have substantial cardioprotective effects against myocardial IRI. However, the transition from these cardioprotective therapies to clinically beneficial therapies for patients with acute myocardial infarction remains elusive. The reasons for the failure of the clinical translation may be multi-faceted, and three points are summarized here: (1) Our understanding of the complex pathophysiological mechanisms of myocardial IRI is far from enough, and the classification of specific therapeutic targets is not rigorous, and not clear enough; (2) Most of the clinical patients have comorbidities, and single cardioprotective strategies including ischemia regulation strategies cannot exert their due cardioprotective effects under conditions of hyperglycemia, hypertension, hyperlipidemia, and aging; (3) Most preclinical experimental results are based on adult, healthy animal models. However, most clinical patients had comorbidities and received multiple drug treatments before reperfusion therapy. In 2019, COST Action proposed a multi-target drug combination initiative for prospective myocardial IRI; the optimal cardioprotective strategy may be a combination of additive or synergistic multi-target therapy, which we support. By establishing more reasonable preclinical models, screening multi-target drug combinations more in line with clinical practice will benefit the translation of clinical treatment strategies.

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Section: Multi-target Strategies For Myocardial Ischemia-reperfusion ...supporting

confidence: 85%

Preclinical multi-target strategies for myocardial ischemia-reperfusion injury

Gao

2022

Front. Cardiovasc. Med.

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“…Apart from cell apoptosis, as a self-protection mechanism of cells under nutrient deficiency conditions, cell autophagy is also discovered to partake in the cardiomyocyte dysfunction during I/R process [ 28 ]. Earlier literatures reported that autophagy plays protective role in the stage of ischemia to against multiple stress, while in the stage of reperfusion, exceeding autophagy will promote cardiomyocyte death [ 29 , 30 ]. The targeted regulation of autophagy via multiple factors, such as mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, and lysosome inhibitors, has been discovered to give cardiomyocytes the ability to resist I/R-resulted cell death [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Myosin 1b Participated in the Modulation of Hypoxia/Reoxygenation-Caused H9c2 Cell Apoptosis and Autophagy

Huang

et al. 2022

Analytical Cellular Pathology

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Myocardial ischemia/reperfusion (I/R) injury seriously threats the health and life of patients with ischemia heart disease. Herein, we probed the potential influence of myosin 1b (myo1b) on hypoxia/reoxygenation- (H/R-) stimulated cardiomyocyte H9c2 cell apoptosis and autophagy. After H/R stimulation, the myo1b mRNA level in H9c2 cells was tested via qRT-PCR. Myo1b overexpression plasmid (OE-myo1b) and small interfering RNA (siRNA) targeting myo1b (si-myo1b) were transfected into H9c2 cells to alter myo1b expression in H9c2 cells. Following H/R stimulation and/or OE-myo1b (or si-myo1b) transfection, H9c2 cell apoptosis, proliferation, and autophagy were detected, respectively. We found that H/R stimulation reduced the mRNA level of myo1b in H9c2 cells and resulted in H9c2 cell apoptosis, proliferation inhibition, and autophagy. Overexpression of myo1b reversed the H/R-resulted H9c2 cell apoptosis, proliferation inhibition, and autophagy. Silence of myo1b had opposite effects, which promoted H9c2 cell apoptosis, reduced cell proliferation, and accelerated cell autophagy. Taken together, Myo1b took part in the modulation of H/R-stimulated cardiomyocyte apoptosis and autophagy, which might be serve as a potential endogenous target for prevention and therapy of I/R injury.

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“…Under physiological conditions or mild stress, autophagy is adaptive and provides cellular quality control for promoting survival. But under chronic or severe stress conditions, insufficient or severe autophagy leads to the accumulation of toxic substances or excessive self-degradation, respectively, both of which are maladaptive and lead to the cell death [ 75 , 76 ]. Increased autophagy in several organs such as the heart has been identified in experimental models of sepsis, but the mechanisms of its occurrence are still unclear [ 77 ].…”

Section: Crucial Role Of Mitochondrial Dysfunction In Sepsismentioning

confidence: 99%

An Overview on Mitochondrial-Based Therapies in Sepsis-Related Myocardial Dysfunction: Mitochondrial Transplantation as a Promising Approach

Mokhtari

Yavari

Badalzadeh

et al. 2022

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Sepsis is defined as a life-threatening organ failure due to dysregulated host response to infection. Despite current advances in our knowledge about sepsis, it is still considered as a major global health challenge. Myocardial dysfunction is a well-defined manifestation of sepsis which is related to worse outcomes in septic patients. Given that the heart is a mitochondria-rich organ and the normal function of mitochondria is essential for successful modulation of septic response, the contribution of mitochondrial damage in sepsis-related myocardial dysfunction has attracted the attention of many scientists. It is widely accepted that mitochondrial damage is involved in sepsis-related myocardial dysfunction; however, effective and potential treatment modalities in clinical setting are still lacking. Mitochondrial-based therapies are potential approaches in sepsis treatment. Although various therapeutic strategies have been used for mitochondrial function improvement, their effects are limited when mitochondria undergo irreversible alterations under septic challenge. Therefore, application of more effective approaches such as mitochondrial transplantation has been suggested. This review highlights the crucial role of mitochondrial damage in sepsis-related myocardial dysfunction, then provides an overview on mitochondrial-based therapies and current approaches to mitochondrial transplantation as a novel strategy, and proposes future directions for more researches in this field.

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The potentials of distinct functions of autophagy to be targeted for attenuation of myocardial ischemia/reperfusion injury in preclinical studies: an up-to-date review

Cited by 20 publications

References 96 publications

Preclinical multi-target strategies for myocardial ischemia-reperfusion injury

Preclinical multi-target strategies for myocardial ischemia-reperfusion injury

Myosin 1b Participated in the Modulation of Hypoxia/Reoxygenation-Caused H9c2 Cell Apoptosis and Autophagy

An Overview on Mitochondrial-Based Therapies in Sepsis-Related Myocardial Dysfunction: Mitochondrial Transplantation as a Promising Approach

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