Evaluating Novel Targets of Ischemia Reperfusion Injury in Pig Models

Baehr, Andrea; Klymiuk, Nikolai; Kupatt, Christian

doi:10.3390/ijms20194749

Cited by 21 publications

(16 citation statements)

References 156 publications

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“…Finally, the size of the heart and coronary arteries makes them adequately suited to study atherosclerosis. Indeed, thrombus formation, plaque ruptures, IR injury and the fact that atherosclerosis develops in older pigs, provides a comparable platform to study the human disease and test therapeutic interventions that can be used in the clinic [ 10 , 167 , 185 ].…”

Section: Other Animal Modelsmentioning

confidence: 99%

Mouse models of atherosclerosis and their suitability for the study of myocardial infarction

Golforoush¹,

Yellon²,

Davidson³

2020

Basic Res Cardiol

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Atherosclerotic plaques impair vascular function and can lead to arterial obstruction and tissue ischaemia. Rupture of an atherosclerotic plaque within a coronary artery can result in an acute myocardial infarction, which is responsible for significant morbidity and mortality worldwide. Prompt reperfusion can salvage some of the ischaemic territory, but ischaemia and reperfusion (IR) still causes substantial injury and is, therefore, a therapeutic target for further infarct limitation. Numerous cardioprotective strategies have been identified that can limit IR injury in animal models, but none have yet been translated effectively to patients. This disconnect prompts an urgent re-examination of the experimental models used to study IR. Since coronary atherosclerosis is the most prevalent morbidity in this patient population, and impairs coronary vessel function, it is potentially a major confounder in cardioprotective studies. Surprisingly, most studies suggest that atherosclerosis does not have a major impact on cardioprotection in mouse models. However, a major limitation of atherosclerotic animal models is that the plaques usually manifest in the aorta and proximal great vessels, and rarely in the coronary vessels. In this review, we examine the commonly used mouse models of atherosclerosis and their effect on coronary artery function and infarct size. We conclude that none of the commonly used strains of mice are ideal for this purpose; however, more recently developed mouse models of atherosclerosis fulfil the requirement for coronary artery lesions, plaque rupture and lipoprotein patterns resembling the human profile, and may enable the identification of therapeutic interventions more applicable in the clinical setting.

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Section: Other Animal Modelsmentioning

confidence: 99%

Mouse models of atherosclerosis and their suitability for the study of myocardial infarction

Golforoush¹,

Yellon²,

Davidson³

2020

Basic Res Cardiol

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“…Despite the clinical importance of I/R injury, bedside treatments that inhibit I/R are still limited, mainly due to the complex mechanisms that contribute to I/R. New pharmacological or molecular interventions that alleviate reperfusion injury are highly desirable for current reperfusion therapy ( Baehr et al, 2019 ; Yu et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy

Lee

Chen

et al. 2020

Front. Pharmacol.

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Myocardial infarction is the leading cause of morbidity and mortality worldwide. Although myocardial reperfusion after ischemia (I/R) is an effective method to save ischemic myocardium, it can cause adverse reactions, including increased oxidative stress and cardiomyocyte apoptosis. Mitochondrial fission and mitophagy are essential factors for mitochondrial quality control, but whether they play key roles in cardiac I/R injury remains unknown. New pharmacological or molecular interventions to alleviate reperfusion injury are currently considered desirable therapies. Vitamin D3 (Vit D3) regulates cardiovascular function, but its physiological role in I/R-exposed hearts, especially its effects on mitochondrial homeostasis, remains unclear. An in vitro hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate myocardial I/R injury. H/R treatment significantly reduced H9c2 cell viability, increased apoptosis, and activated caspase 3. In addition, H/R treatment increased mitochondrial fission, as manifested by increased expression of phosphorylated dynein-related protein 1 (p-Drp1) and mitochondrial fission factor (Mff) as well as increased mitochondrial translocation of Drp1. Treatment with the mitochondrial reactive oxygen species scavenger MitoTEMPO increased cell viability and decreased mitochondrial fission. H/R conditions elicited excessive mitophagy, as indicated by increased expression of BCL2-interacting protein 3 (BNIP3) and light chain (LC3BII/I) and increased formation of autolysosomes. In contrast, Vit D3 reversed these effects. In a mouse model of I/R, apoptosis, mitochondrial fission, and mitophagy were induced. Vit D3 treatment mitigated apoptosis, mitochondrial fission, mitophagy, and myocardial ultrastructural abnormalities. The results indicate that Vit D3 exerts cardioprotective effects against I/R cardiac injury by protecting mitochondrial structural and functional integrity and reducing mitophagy.

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“…Efforts to target the oxidative insult that occurs immediately following IR using therapies such as antioxidants have proven unsuccessful (Baehr et al, 2019). The current study provides novel data demonstrating that navitoclax mediates elimination of the senescence that occurs downstream of oxidative stress and that this reduces scar size, increases angiogenesis, and improves cardiac function.…”

Section: Discussionmentioning

confidence: 99%

Clearance of senescent cells during cardiac ischemia–reperfusion injury improves recovery

et al. 2020

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Evaluating Novel Targets of Ischemia Reperfusion Injury in Pig Models

Cited by 21 publications

References 156 publications

Mouse models of atherosclerosis and their suitability for the study of myocardial infarction

Mouse models of atherosclerosis and their suitability for the study of myocardial infarction

Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy

Clearance of senescent cells during cardiac ischemia–reperfusion injury improves recovery

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