scholarly journals Noninvasive approach to mend the broken heart: Is “remote conditioning” a promising strategy for application in humans?

2017 ◽  
Vol 95 (10) ◽  
pp. 1204-1212 ◽  
Author(s):  
Táňa Ravingerová ◽  
Veronika Farkašová ◽  
Lucia Griecsová ◽  
Martina Muráriková ◽  
Slavka Carnická ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cost Effective ◽  
Neural Pathways ◽  
Protective Mechanisms ◽  
Clinical Role ◽  
Technical Requirements ◽  
Promising Strategy ◽  
Remote Organ ◽  
Local Stimulus

Currently, there are no satisfactory interventions to protect the heart against the detrimental effects of ischemia–reperfusion injury. Although ischemic preconditioning (PC) is the most powerful form of intrinsic cardioprotection, its application in humans is limited to planned interventions, due to its short duration and technical requirements. However, many organs/tissues are capable of producing “remote” PC (RPC) when subjected to brief bouts of ischemia–reperfusion. RPC was first described in the heart where brief ischemia in one territory led to protection in other area. Later on, RPC started to be used in patients with acute myocardial infarction, albeit with ambiguous results. It is hypothesized that the connection between the signal triggered in remote organ and protection induced in the heart can be mediated by humoral and neural pathways, as well as via systemic response to short sublethal ischemia. However, although RPC has a potentially important clinical role, our understanding of the mechanistic pathways linking the local stimulus to the remote organ remains incomplete. Nevertheless, RPC appears as a cost-effective and easily performed intervention. Elucidation of protective mechanisms activated in the remote organ may have therapeutic and diagnostic implications in the management of myocardial ischemia and lead to development of pharmacological RPC mimetics.

scholarly journals Diabetic Inhibition of Preconditioning- and Postconditioning-Mediated Myocardial Protection against Ischemia/Reperfusion Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Xia Yin ◽  
Yang Zheng ◽  
Xujie Zhai ◽  
Xin Zhao ◽  
Lu Cai
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Protective Effect ◽  
Myocardial Protection ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Patients ◽  
Protective Mechanisms ◽  
Gsk 3Β ◽  
Pathogenic Effects

Ischemic preconditioning (IPC) or postconditioning (Ipost) is proved to efficiently prevent ischemia/reperfusion injuries. Mortality of diabetic patients with acute myocardial infarction was found to be 2–6 folds higher than that of non-diabetic patients with same myocardial infarction, which may be in part due to diabetic inhibition of IPC- and Ipost-mediated protective mechanisms. Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3β pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore, this review briefly introduced the general features of IPC- and Ipost-mediated myocardial protection and the general pathogenic effects of diabetes on the myocardium. We have collected experimental evidence that indicates the diabetic inhibition of IPC- and Ipost-mediated myocardial protection. Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore any strategy to activate PI3K/Akt and associated GSK-3β pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries.

Bioinspired cell-derived nanovesicles protect the heart from ischemia reperfusion injury

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Wang ◽  
C.Y Huang ◽  
Y.R Neupane ◽  
X Wang ◽  
O Zharkova ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Cell Apoptosis ◽  
Imaging System ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Cost Effective ◽  
Public Institution ◽  
Funding Source ◽  
Myocardial Infarct Size

Abstract Introduction Exosomes have been proven to alleviate myocardial ischemia reperfusion (I/R) injury in preclinical studies. However, the laborious and low-yield production process of naturally secreted exosomes has been impeding their translation into clinical trials. Purpose We aim to develop a simple and cost-effective protocol to produce exosome mimetics, bioinspired Cell-Derived Nanovesicles (CDNs), and examine their intrinsic bioactivity in a mouse model of I/R injury. Methods CDNs were produced from human U937 monocytes using cell shearing approach and characterized by dynamic light scattering (DLS), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Lipid composition of cells and CDNs was analysed by lipidomics. I/R injury was induced by transient occlusion of left coronary artery. Data was analysed with Mann-Whitney U test. P<0.05 was considered statically significant. Results We obtained 538 mg (protein content) of CDNs, or 3x109 CDNs, via cell shearing approach from 2×107 cells, approximately 15 folds of exosomes via natural secretion from the same number of cells. CDNs were 125±8 nm in diameter with negative surface charge (zeta potential −7.0±0.8) and presented as double-membranous vesicles under TEM. In vitro, CDNs showed strong antioxidant activity and could be taken up by bone marrow-derived macrophages. Following intravenous administration, as demonstrated by the IVIS Spectrum imaging system, CDNs accumulated specifically in the infarct area of the heart within 3 hours. Compared with saline treatment, CDNs reduced myocardial infarct size by 31.6% (p<0.01) after 24 hours of I/R injury. Intriguingly, CDNs generated from human mesenchymal stem cells showed similar therapeutic efficacy. Mechanistically, CDNs inhibited infiltration of inflammatory cells (macrophages) and promoted upregulation of the anti-inflammatory cytokine interleukin 10 (IL10) in the I/R injured hearts. In the blood stream, CDNs increased IL10 protein level and exerted antioxidant activity. Furthermore, CDNs reduced I/R injury-induced cell apoptosis in the myocardium. Conclusion We have established a cost-effective approach to produce exosome mimetics, bioinspired CDNs, which protect the heart from I/R injury via inhibition of inflammation, oxidative stress and cardiac cell apoptosis. CDNs have intrinsic cardioprotective capability in heart injury, comparable to exosomes. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National University Health System.

scholarly journals Ischemic Postconditioning as a Novel Avenue to Protect against Brain Injury after Stroke

2009 ◽  
Vol 29 (5) ◽  
pp. 873-885 ◽  
Author(s):  
Heng Zhao
Keyword(s):  
Protein Kinase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Postconditioning ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Mitogen Activated Protein ◽  
Cerebral Ischemic

Ischemic postconditioning initially referred to a stuttering reperfusion performed immediately after reperfusion, for preventing ischemia/reperfusion injury in both myocardial and cerebral infarction. It has evolved into a concept that can be induced by a broad range of stimuli or triggers, and may even be performed as late as 6 h after focal ischemia and 2 days after transient global ischemia. The concept is thought to be derived from ischemic preconditioning or partial/gradual reperfusion, but in fact the first experiment for postconditioning was carried out much earlier than that of preconditioning or partial/gradual reperfusion, in the research on myocardial ischemia. This review first examines the protective effects and parameters of postconditioning in various cerebral ischemic models. Thereafter, it provides insights into the protective mechanisms of postconditioning associated with reperfusion injury and the Akt, mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and ATP-sensitive K+ (KATP) channel cell signaling pathways. Finally, some open issues and future challenges regarding clinical translation of postconditioning are discussed.

Aliskiren – a promising strategy for ovarian ischemia/reperfusion injury protection in rats via RAAS

2016 ◽  
Vol 32 (8) ◽  
pp. 675-683 ◽  
Author(s):  
Yasin Bayir ◽  
Elif Cadirci ◽  
Beyzagul Polat ◽  
Nurcan Kilic Baygutalp ◽  
Abdulmecit Albayrak ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Promising Strategy ◽  
Injury Protection

Increased superoxide formation induced by irradiation preconditioning triggers kidney resistance to ischemia-reperfusion injury in mice

2009 ◽  
Vol 296 (5) ◽  
pp. F1202-F1211 ◽  
Author(s):  
Jinu Kim ◽  
Jeen-Woo Park ◽  
Kwon Moo Park
Keyword(s):  
Superoxide Dismutase ◽  
Structural Damage ◽  
Manganese Superoxide Dismutase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Mechanisms ◽  
Hsp 27 ◽  
Superoxide Formation ◽  
Cesium 137 ◽  
Mnsod Activity

One of the obstacles in irradiation therapy is cytoresistance, acquired by activation of self-defense systems, such as antioxidant or molecular chaperone systems, to cope with stress. We investigated whether irradiation preconditioning (IP) rendered resistance of the kidney against subsequent ischemia-reperfusion (I/R) and attempted to elucidate any such protective mechanisms. Mice were irradiated with a total of 4, 6, or 8 Gy using a cesium-137 source irradiator and then, 6 days later, were subjected to 28 min of bilateral renal ischemia followed by reperfusion. Eight Gy of IP significantly attenuated the increases in plasma creatinine (PCr) and blood urea nitrogen (BUN) concentration, structural damage, lipid peroxidation, superoxide formation, expression and activity of NADPH oxidase (NOX)-2, nitrotyrosine level, and hydrogen peroxide production after I/R in kidney tissues, indicating that IP protects the kidneys from I/R injury. IP markedly increased the activity of NOX, resulting in increased superoxide formation, manganese superoxide dismutase (MnSOD) activity and expression, and heat shock protein (HSP)-27 expression in kidneys. However, it did not change expressions of catalase, copper-zinc superoxide dismutase (CuZnSOD), and HSP-72. To investigate whether the protection afforded by IP was associated with increases in MnSOD and HSP-27 expression triggered by increased superoxide formation after IP, we administered manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin, a superoxide scavenger, to IP mice. This administration blocked superoxide formation and subsequent increases in MnSOD and HSP-27 expression and accelerated the post-I/R increases in PCr and BUN. In conclusion, IP renders kidney resistance to I/R injury, and this resistance is mediated by increased superoxide formation, which activates MnSOD activity and expression as well as HSP-27 expression.

scholarly journals Ferroptosis and its facet in Cancer therapy

2021 ◽  
Vol 6 (1) ◽  
pp. 10-15
Author(s):  
Shreya Shreshtha
Keyword(s):  
Cell Death ◽  
Cell Therapy ◽  
Cancer Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Death Process ◽  
Cell Organelles ◽  
Clinical Role ◽  
Cell Death Process

Ferroptosis is a regulated process impelled by iron-dependent lipid peroxidation. It is a new type of cell destruction processes including apoptosis, autophagy and necrosis. It demonstrates mainly the contraction of mitochondria and expansion of mitochondrial membrane density which does not lead to any alteration in morphology. Due to the malfunctioning of ferroptosis several disorders arise which includes damage of one or more nerve which leads to numbness and muscle weakness whereas ischemia reperfusion injury, acute kidney failure and cancer also occurs. Also, ferroptosis is induced in large number of cancer cells through series of small molecules which helps in to bringing out this process. In scientific research and medicine many findings contribute in the chance of defeating cancer by genetic or pharmacological interference with ferroptosis cell death which is appealing for various researches. There are multiple pathways and cell organelles which plays a role in ferroptosis regulation. Ongoing studies on ferroptosis have demonstrated its role in humans though its mechanism is not yet clear. Recently, various studies have encouraged the role of this newly emerged cell death process and also showed some effective usage in the treatment of cancer. Here, we review the mitochondrial aspect of ferroptosis as well as discuss on the role of ferroptosis in Cancer cell therapy. We will also aim on the future scope of ferroptosis in the treatment of Cancer as well as discuss about the problems related to its clinical role which may trigger the cancer cell therapy.

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