Extracellular RNA, a Potential Drug Target for Alleviating Atherosclerosis, Ischemia/Reperfusion Injury and Organ Transplantation

2019 ◽  
Vol 19 (15) ◽  
pp. 1189-1195 ◽  
Author(s):  
Anna-Kristina Kluever ◽  
Elisabeth Deindl
Keyword(s):  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Drug Target ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Extracellular Rna

Mitochondrial Aldehyde Dehydrogenase, A Potential Drug Target for Protection of Heart and Brain from Ischemia/Reperfusion Injury

2014 ◽  
Vol 15 (10) ◽  
pp. 948-955 ◽  
Author(s):  
Xiu-Ju Luo ◽  
Bin Liu ◽  
Qi-Lin Ma ◽  
Jun Peng
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Drug Target ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Beneficial Effects ◽  
Therapeutic Value

Mitochondrial aldehyde dehydrogenase (ALDH2) is an isoenzyme of aldehyde dehydrogenases (ALDH), a group of enzymes that are responsible for clearance of aldehydes in the body. In animal myocardial or cerebral ischemia/ reperfusion (I/R) models, accumulation of toxic aldehydes, such as 4-hydroxy-2-nonenal and malondialdehyde, is thought to be an important mechanism for myocardial and cerebral I/R injury. Among the isoenzymes of ALDH, ALDH2 is believed to play a major role in clearance of toxic aldehydes. Thus, ALDH2 might be a potential drug target for protection of the heart or brain from I/R injury. Indeed, some of the newly identified ALDH2 activators (such as Alda-1) have demonstrated beneficial effects on heart and brain I/R injury. In addition, ALDH activity is present at high levels in some stem or progenitor cells, known as ALDH bright (ALDHbr) cells, which possess potential value in treating patients with myocardial ischemia. The main purpose of this review is 1) to summarize recent findings regarding the role of ALDH2 in protection of heart or brain from I/R injury, 2) to list the available ALDH2 activators with their potency, selectivity and clinical potentials, and 3) to provide a rationale for ALDHbr cells in clinical therapeutic value.

scholarly journals Review: Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation

2020 ◽  
Vol 21 (22) ◽  
pp. 8549
Author(s):  
André Renaldo Fernández ◽  
Rodrigo Sánchez-Tarjuelo ◽  
Paolo Cravedi ◽  
Jordi Ochando ◽  
Marcos López-Hoyos
Keyword(s):  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Loss ◽  
Surgical Techniques ◽  
Immunosuppressive Drugs ◽  
Donation Process ◽  
End Stage ◽  
Significant Injury

Thanks to the development of new, more potent and selective immunosuppressive drugs together with advances in surgical techniques, organ transplantation has emerged from an experimental surgery over fifty years ago to being the treatment of choice for many end-stage organ diseases, with over 139,000 organ transplants performed worldwide in 2019. Inherent to the transplantation procedure is the fact that the donor organ is subjected to blood flow cessation and ischemia during harvesting, which is followed by preservation and reperfusion of the organ once transplanted into the recipient. Consequently, ischemia/reperfusion induces a significant injury to the graft with activation of the immune response in the recipient and deleterious effect on the graft. The purpose of this review is to discuss and shed new light on the pathways involved in ischemia/reperfusion injury (IRI) that act at different stages during the donation process, surgery, and immediate post-transplant period. Here, we present strategies that combine various treatments targeted at different mechanistic pathways during several time points to prevent graft loss secondary to the inflammation caused by IRI.

scholarly journals Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review

2020 ◽  
Vol 21 (2) ◽  
pp. 631 ◽  
Author(s):  
Lina Jakubauskiene ◽  
Matas Jakubauskas ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Positive Impact ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Comprehensive Review ◽  
Long Term Treatment

In recent decades, solid organ transplantation (SOT) has increased the survival and quality of life for patients with end-stage organ failure by providing a potentially long-term treatment option. Although the availability of organs for transplantation has increased throughout the years, the demand greatly outweighs the supply. One possible solution for this problem is to extend the potential donor pool by using extended criteria donors. However, organs from such donors are more prone to ischemia reperfusion injury (IRI) resulting in higher rates of delayed graft function, acute and chronic graft rejection and worse overall SOT outcomes. This can be overcome by further investigating donor preconditioning strategies, graft perfusion and storage and by finding novel therapeutic agents that could reduce IRI. relaxin (RLX) is a peptide hormone with antifibrotic, antioxidant, anti-inflammatory and cytoprotective properties. The main research until now focused on heart failure; however, several preclinical studies showed its potentials for reducing IRI in SOT. The aim of this comprehensive review is to overview currently available literature on the possible role of RLX in reducing IRI and its positive impact on SOT.

scholarly journals Medical Gases: A Novel Strategy for Attenuating Ischemia—Reperfusion Injury in Organ Transplantation?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Arunotai Siriussawakul ◽  
Lucinda I. Chen ◽  
John D. Lang
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Organ Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inhaled Nitric Oxide ◽  
Clinical Consequence ◽  
Solid Organ

Ischemia reperfusion injury (IRI) is an inevitable clinical consequence in organ transplantation. It can lead to early graft nonfunction and contribute to acute and chronic graft rejection. Advanced molecular biology has revealed the highly complex nature of this phenomenon and few definitive therapies exist. This paper reviews factors involved in the pathophysiology of IRI and potential ways to attenuate it. In recent years, inhaled nitric oxide, carbon monoxide, and hydrogen sulfide have been increasingly explored as plausible novel medical gases that can attenuate IRI via multiple mechanisms, including microvascular vasorelaxation, reduced inflammation, and mitochondrial modulation. Here, we review recent advances in research utilizing inhaled nitric oxide, carbon monoxide, and hydrogen sulfide in animal and human studies of IRI and postulate on its future applications specific to solid organ transplantation.

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